[ { "key": "JD84RSN9", "version": 11, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/JD84RSN9", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/JD84RSN9", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Wilke et al.", "parsedDate": "2011-03", "numChildren": 0 }, "data": { "key": "JD84RSN9", "version": 11, "itemType": "journalArticle", "title": "The emerging role of electronic medical records in pharmacogenomics", "creators": [ { "creatorType": "author", "firstName": "R A", "lastName": "Wilke" }, { "creatorType": "author", "firstName": "H", "lastName": "Xu" }, { "creatorType": "author", "firstName": "J C", "lastName": "Denny" }, { "creatorType": "author", "firstName": "D M", "lastName": "Roden" }, { "creatorType": "author", "firstName": "R M", "lastName": "Krauss" }, { "creatorType": "author", "firstName": "C A", "lastName": "McCarty" }, { "creatorType": "author", "firstName": "R L", "lastName": "Davis" }, { "creatorType": "author", "firstName": "T", "lastName": "Skaar" }, { "creatorType": "author", "firstName": "J", "lastName": "Lamba" }, { "creatorType": "author", "firstName": "G", "lastName": "Savova" } ], "abstractNote": "Health-care information technology and genotyping technology are both advancing rapidly, creating new opportunities for medical and scientific discovery. The convergence of these two technologies is now facilitating genetic association studies of unprecedented size within the context of routine clinical care. As a result, the medical community will soon be presented with a number of novel opportunities to bring functional genomics to the bedside in the area of pharmacotherapy. By linking biological material to comprehensive medical records, large multi-institutional biobanks are now poised to advance the field of pharmacogenomics through three distinct mechanisms: (i) retrospective assessment of previously known findings in a clinical practice-based setting, (ii) discovery of new associations in huge observational cohorts, and (iii) prospective application in a setting capable of providing real-time decision support. This review explores each of these translational mechanisms within a historical framework.", "publicationTitle": "Clinical pharmacology and therapeutics", "publisher": "", "place": "", "date": "Mar 2011", "volume": "89", "issue": "3", "section": "", "partNumber": "", "partTitle": "", "pages": "379-386", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Clin. Pharmacol. Ther.", "DOI": "10.1038/clpt.2010.260", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/21248726", "accessDate": "2012-07-13T17:58:46Z", "PMID": "", "PMCID": "", "ISSN": "1532-6535", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 21248726", "tags": [ { "tag": "Decision Support Techniques", "type": 1 }, { "tag": "Electronic Health Records", "type": 1 }, { "tag": "Genetic Association Studies", "type": 1 }, { "tag": "Genomics", "type": 1 }, { "tag": "Genotype", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Pharmaceutical Preparations", "type": 1 }, { "tag": "Pharmacogenetics", "type": 1 }, { "tag": "Research Design", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-07-13T17:58:46Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "WAUUW7JZ", "version": 11, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/WAUUW7JZ", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/WAUUW7JZ", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Gardner", "parsedDate": "2004-06", "numChildren": 0 }, "data": { "key": "WAUUW7JZ", "version": 11, "itemType": "journalArticle", "title": "Using genomics to help predict drug interactions", "creators": [ { "creatorType": "author", "firstName": "Donald", "lastName": "Gardner" } ], "abstractNote": "This article proposes using genomic information to help tailor the output of a drug interaction program for a patient. This paper focuses on a particular CYP450 enzyme to illustrate adding genomic information to an existing drug interaction database. The data are formatted as an Extensible Markup Language (XML) document. The additional interaction information based on genomics for a patient is added to an XML document using XML tags. The suggestion is to combine specifics about a patient's genome with genomic information in the drug interactions database to increase the accuracy and details of a drug interaction program.", "publicationTitle": "Journal of biomedical informatics", "publisher": "", "place": "", "date": "Jun 2004", "volume": "37", "issue": "3", "section": "", "partNumber": "", "partTitle": "", "pages": "139-146", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J Biomed Inform", "DOI": "10.1016/j.jbi.2004.05.001", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/15196479", "accessDate": "2012-07-13T17:04:37Z", "PMID": "", "PMCID": "", "ISSN": "1532-0464", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 15196479", "tags": [ { "tag": "Aryl Hydrocarbon Hydroxylases", "type": 1 }, { "tag": "Database Management Systems", "type": 1 }, { "tag": "Databases, Factual", "type": 1 }, { "tag": "Decision Support Systems, Clinical", "type": 1 }, { "tag": "Drug Interactions", "type": 1 }, { "tag": "Drug Therapy, Computer-Assisted", "type": 1 }, { "tag": "Gene Expression Profiling", "type": 1 }, { "tag": "Genetic Predisposition to Disease", "type": 1 }, { "tag": "Genetic Testing", "type": 1 }, { "tag": "Genomics", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Hypermedia", "type": 1 }, { "tag": "Information Storage and Retrieval", "type": 1 }, { "tag": "Medical Errors", "type": 1 }, { "tag": "Medical Records Systems, Computerized", "type": 1 }, { "tag": "Mixed Function Oxygenases", "type": 1 }, { "tag": "Programming Languages", "type": 1 }, { "tag": "Registries", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-07-13T17:04:37Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "I2TETGCH", "version": 11, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/I2TETGCH", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/I2TETGCH", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "de Leon et al.", "parsedDate": "2009-06", "numChildren": 0 }, "data": { "key": "I2TETGCH", "version": 11, "itemType": "journalArticle", "title": "Pharmacokinetic drug interaction studies must consider pharmacological heterogeneity, use of repeated dosing, and translation into a message understandable to practicing clinicians", "creators": [ { "creatorType": "author", "firstName": "Jose", "lastName": "de Leon" }, { "creatorType": "author", "firstName": "Edoardo", "lastName": "Spina" }, { "creatorType": "author", "firstName": "Francisco J", "lastName": "Diaz" } ], "abstractNote": "", "publicationTitle": "Journal of clinical psychopharmacology", "publisher": "", "place": "", "date": "Jun 2009", "volume": "29", "issue": "3", "section": "", "partNumber": "", "partTitle": "", "pages": "201-205", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J Clin Psychopharmacol", "DOI": "10.1097/JCP.0b013e3181a497f1", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/19440070", "accessDate": "2012-06-19T18:04:36Z", "PMID": "", "PMCID": "", "ISSN": "1533-712X", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 19440070", "tags": [ { "tag": "Clinical Trials as Topic", "type": 1 }, { "tag": "Drug Administration Schedule", "type": 1 }, { "tag": "Drug Interactions", "type": 1 }, { "tag": "Guidelines as Topic", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Models, Biological", "type": 1 }, { "tag": "Pharmaceutical Preparations", "type": 1 }, { "tag": "Pharmacokinetics", "type": 1 }, { "tag": "United States", "type": 1 }, { "tag": "United States Food and Drug Administration", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-06-19T18:04:36Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "WC45HT3H", "version": 10, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/WC45HT3H", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/WC45HT3H", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Nelson et al.", "parsedDate": "2011-08", "numChildren": 0 }, "data": { "key": "WC45HT3H", "version": 10, "itemType": "journalArticle", "title": "Normalized names for clinical drugs: RxNorm at 6 years", "creators": [ { "creatorType": "author", "firstName": "Stuart J", "lastName": "Nelson" }, { "creatorType": "author", "firstName": "Kelly", "lastName": "Zeng" }, { "creatorType": "author", "firstName": "John", "lastName": "Kilbourne" }, { "creatorType": "author", "firstName": "Tammy", "lastName": "Powell" }, { "creatorType": "author", "firstName": "Robin", "lastName": "Moore" } ], "abstractNote": "OBJECTIVE\n\nIn the 6 years since the National Library of Medicine began monthly releases of RxNorm, RxNorm has become a central resource for communicating about clinical drugs and supporting interoperation between drug vocabularies.\n\n\nMATERIALS AND METHODS\n\nBuilt on the idea of a normalized name for a medication at a given level of abstraction, RxNorm provides a set of names and relationships based on 11 different external source vocabularies. The standard model enables decision support to take place for a variety of uses at the appropriate level of abstraction. With the incorporation of National Drug File Reference Terminology (NDF-RT) from the Veterans Administration, even more sophisticated decision support has become possible.\n\n\nDISCUSSION\n\nWhile related products such as RxTerms, RxNav, MyMedicationList, and MyRxPad have been recognized as helpful for various uses, tasks such as identifying exactly what is and is not on the market remain a challenge.", "publicationTitle": "Journal of the American Medical Informatics Association: JAMIA", "publisher": "", "place": "", "date": "2011 Jul-Aug", "volume": "18", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "441-448", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J Am Med Inform Assoc", "DOI": "10.1136/amiajnl-2011-000116", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/21515544", "accessDate": "2012-09-27T09:27:36Z", "PMID": "", "PMCID": "", "ISSN": "1527-974X", "archive": "", "archiveLocation": "", "shortTitle": "Normalized names for clinical drugs", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 21515544", "tags": [ { "tag": "Decision Support Systems, Clinical", "type": 1 }, { "tag": "Drug Information Services", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Information Storage and Retrieval", "type": 1 }, { "tag": "National Library of Medicine (U.S.)", "type": 1 }, { "tag": "Pharmaceutical Preparations", "type": 1 }, { "tag": "Terminology as Topic", "type": 1 }, { "tag": "United States", "type": 1 }, { "tag": "User-Computer Interface", "type": 1 }, { "tag": "Vocabulary, Controlled", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-10-02T17:55:58Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "W9G3JHKJ", "version": 10, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/W9G3JHKJ", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/W9G3JHKJ", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Duke et al.", "parsedDate": "2011-05-23", "numChildren": 0 }, "data": { "key": "W9G3JHKJ", "version": 10, "itemType": "journalArticle", "title": "A quantitative analysis of adverse events and \"overwarning\" in drug labeling", "creators": [ { "creatorType": "author", "firstName": "Jon", "lastName": "Duke" }, { "creatorType": "author", "firstName": "Jeff", "lastName": "Friedlin" }, { "creatorType": "author", "firstName": "Patrick", "lastName": "Ryan" } ], "abstractNote": "", "publicationTitle": "Archives of internal medicine", "publisher": "", "place": "", "date": "May 23, 2011", "volume": "171", "issue": "10", "section": "", "partNumber": "", "partTitle": "", "pages": "944-946", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Arch. Intern. Med.", "DOI": "10.1001/archinternmed.2011.182", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/21606101", "accessDate": "2012-09-21T18:08:46Z", "PMID": "", "PMCID": "", "ISSN": "1538-3679", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 21606101", "tags": [ { "tag": "Adverse Drug Reaction Reporting Systems", "type": 1 }, { "tag": "Drug Labeling", "type": 1 }, { "tag": "Evaluation Studies as Topic", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Product Surveillance, Postmarketing", "type": 1 }, { "tag": "Total Quality Management", "type": 1 }, { "tag": "United States", "type": 1 }, { "tag": "United States Food and Drug Administration", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-10-02T17:55:58Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "J8D7QF5G", "version": 10, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/J8D7QF5G", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/J8D7QF5G", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Hines et al.", "parsedDate": "2011-05-15", "numChildren": 0 }, "data": { "key": "J8D7QF5G", "version": 10, "itemType": "journalArticle", "title": "Critical issues associated with drug-drug interactions: highlights of a multistakeholder conference", "creators": [ { "creatorType": "author", "firstName": "Lisa E", "lastName": "Hines" }, { "creatorType": "author", "firstName": "John E", "lastName": "Murphy" }, { "creatorType": "author", "firstName": "Amy J", "lastName": "Grizzle" }, { "creatorType": "author", "firstName": "Daniel C", "lastName": "Malone" } ], "abstractNote": "", "publicationTitle": "American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists", "publisher": "", "place": "", "date": "May 15, 2011", "volume": "68", "issue": "10", "section": "", "partNumber": "", "partTitle": "", "pages": "941-946", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Am J Health Syst Pharm", "DOI": "10.2146/ajhp100440", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/21546646", "accessDate": "2012-07-14T14:15:41Z", "PMID": "", "PMCID": "", "ISSN": "1535-2900", "archive": "", "archiveLocation": "", "shortTitle": "Critical issues associated with drug-drug interactions", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 21546646", "tags": [ { "tag": "Congresses as Topic", "type": 1 }, { "tag": "Decision Support Systems, Clinical", "type": 1 }, { "tag": "Drug Interactions", "type": 1 }, { "tag": "Medical Order Entry Systems", "type": 1 }, { "tag": "Medication Errors", "type": 1 }, { "tag": "Safety Management", "type": 1 } ], "collections": [], "relations": { "owl:sameAs": "http://zotero.org/groups/14236/items/PG4BB8QR" }, "dateAdded": "2012-07-14T14:15:41Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "9SRN8XNA", "version": 10, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/9SRN8XNA", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/9SRN8XNA", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Skinner et al.", "parsedDate": "2003-03", "numChildren": 0 }, "data": { "key": "9SRN8XNA", "version": 10, "itemType": "journalArticle", "title": "Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers", "creators": [ { "creatorType": "author", "firstName": "Michael H", "lastName": "Skinner" }, { "creatorType": "author", "firstName": "Han-Yi", "lastName": "Kuan" }, { "creatorType": "author", "firstName": "Alan", "lastName": "Pan" }, { "creatorType": "author", "firstName": "Korbtham", "lastName": "Sathirakul" }, { "creatorType": "author", "firstName": "Mary Pat", "lastName": "Knadler" }, { "creatorType": "author", "firstName": "Celedon R", "lastName": "Gonzales" }, { "creatorType": "author", "firstName": "Kwee Poo", "lastName": "Yeo" }, { "creatorType": "author", "firstName": "Shobha", "lastName": "Reddy" }, { "creatorType": "author", "firstName": "Maggie", "lastName": "Lim" }, { "creatorType": "author", "firstName": "Mosun", "lastName": "Ayan-Oshodi" }, { "creatorType": "author", "firstName": "Stephen D", "lastName": "Wise" } ], "abstractNote": "BACKGROUND AND OBJECTIVES\n\nDuloxetine, a potent dual reuptake inhibitor of serotonin and norepinephrine currently undergoing clinical investigation for treatment of depression and stress urinary incontinence, has the potential to act as both a substrate and an inhibitor of cytochrome P4502D6 (CYP2D6). Our objectives were to determine the effect of duloxetine on the pharmacokinetics of desipramine, a tricyclic antidepressant metabolized by CYP2D6 (study 1), and the effect of paroxetine, a potent CYP2D6 inhibitor, on duloxetine pharmacokinetics (study 2).\n\n\nMETHODS\n\nSubjects were healthy men and women between 21 and 63 years old. All subjects were genotypically CYP2D6 extensive metabolizers. In study 1, 50 mg of desipramine was administered as a single dose alone and in the presence of steady-state duloxetine 60 mg twice daily. In study 2, steady-state pharmacokinetics of duloxetine 40 mg once daily were determined in the presence and absence of steady-state paroxetine 20 mg once daily.\n\n\nRESULTS\n\nDuloxetine increased the maximum plasma concentration of desipramine 1.7-fold and the area under the concentration-time curve 2.9-fold. Paroxetine increased the maximum plasma concentration of duloxetine and the area under the concentration-time curve at steady state 1.6-fold. Reports of adverse events were similar whether duloxetine was administered alone or in combination with desipramine or paroxetine.\n\n\nCONCLUSION\n\nDuloxetine 60 mg twice daily is a moderately potent CYP2D6 inhibitor, intermediate between paroxetine and sertraline. The potent CYP2D6 inhibitor paroxetine has a moderate effect on duloxetine concentrations. The results of these 2 studies suggest that caution should be used when CYP2D6 substrates and inhibitors are coadministered with duloxetine.", "publicationTitle": "Clinical pharmacology and therapeutics", "publisher": "", "place": "", "date": "Mar 2003", "volume": "73", "issue": "3", "section": "", "partNumber": "", "partTitle": "", "pages": "170-177", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Clin. Pharmacol. Ther.", "DOI": "10.1067/mcp.2003.28", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/12621382", "accessDate": "2012-07-13T21:34:57Z", "PMID": "", "PMCID": "", "ISSN": "0009-9236", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 12621382", "tags": [ { "tag": "Adult", "type": 1 }, { "tag": "Antidepressive Agents, Tricyclic", "type": 1 }, { "tag": "Area Under Curve", "type": 1 }, { "tag": "Cytochrome P-450 CYP2D6", "type": 1 }, { "tag": "Desipramine", "type": 1 }, { "tag": "Drug Administration Schedule", "type": 1 }, { "tag": "Drug Interactions", "type": 1 }, { "tag": "Female", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Middle Aged", "type": 1 }, { "tag": "Paroxetine", "type": 1 }, { "tag": "Reference Values", "type": 1 }, { "tag": "Serotonin Uptake Inhibitors", "type": 1 }, { "tag": "Thiophenes", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-07-13T21:34:57Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "KR6JSFDA", "version": 10, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/KR6JSFDA", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/KR6JSFDA", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Lobo et al.", "parsedDate": "2008", "numChildren": 0 }, "data": { "key": "KR6JSFDA", "version": 10, "itemType": "journalArticle", "title": "In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine", "creators": [ { "creatorType": "author", "firstName": "Evelyn D", "lastName": "Lobo" }, { "creatorType": "author", "firstName": "Richard F", "lastName": "Bergstrom" }, { "creatorType": "author", "firstName": "Shobha", "lastName": "Reddy" }, { "creatorType": "author", "firstName": "Tonya", "lastName": "Quinlan" }, { "creatorType": "author", "firstName": "Jill", "lastName": "Chappell" }, { "creatorType": "author", "firstName": "Quan", "lastName": "Hong" }, { "creatorType": "author", "firstName": "Barbara", "lastName": "Ring" }, { "creatorType": "author", "firstName": "Mary Pat", "lastName": "Knadler" } ], "abstractNote": "OBJECTIVE\n\nTo determine whether duloxetine is a substrate, inhibitor or inducer of cytochrome P450 (CYP) 1A2 enzyme, using in vitro and in vivo studies in humans.\n\n\nMETHODS\n\nHuman liver microsomes or cells with expressed CYP enzymes and specific CYP inhibitors were used to identify which CYP enzymes catalyse the initial oxidation steps in the metabolism of duloxetine. The potential of duloxetine to inhibit CYP1A2 activity was determined using incubations with human liver microsomes and phenacetin, the CYP1A2 substrate. The potential for duloxetine to induce CYP1A2 activity was determined using human primary hepatocytes treated with duloxetine for 72 hours. Studies in humans were conducted using fluvoxamine, a potent CYP1A2 inhibitor, and theophylline, a CYP1A2 substrate, as probes. The subjects were healthy men and women aged 18-65 years. Single-dose duloxetine was administered either intravenously as a 10-mg infusion over 30 minutes or orally as a 60-mg dose in the presence or absence of steady-state fluvoxamine (100 mg orally once daily). Single-dose theophylline was given as 30-minute intravenous infusions of aminophylline 250 mg in the presence or absence of steady-state duloxetine (60 mg orally twice daily). Plasma concentrations of duloxetine, its metabolites and theophylline were determined using liquid chromatography with tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods and evaluated using mixed-effects ANOVA. Safety measurements included vital signs, clinical laboratory tests, a physical examination, ECG readings and adverse event reports.\n\n\nRESULTS\n\nThe in vitro results indicated that duloxetine is metabolized by CYP1A2; however, duloxetine was predicted not to be an inhibitor or inducer of CYP1A2 in humans. Following oral administration in the presence of fluvoxamine, the duloxetine area under the plasma concentration-time curve from time zero to infinity (AUC(infinity)) and the maximum plasma drug concentration (C(max)) significantly increased by 460% (90% CI 359, 584) and 141% (90% CI 93, 200), respectively. In the presence of fluvoxamine, the oral bioavailability of duloxetine increased from 42.8% to 81.9%. In the presence of duloxetine, the theophylline AUC(infinity) and C(max) increased by only 13% (90% CI 7, 18) and 7% (90% CI 2, 14), respectively. Coadministration of duloxetine with fluvoxamine or theophylline did not result in any clinically important safety concerns, and these combinations were generally well tolerated.\n\n\nCONCLUSION\n\nDuloxetine is metabolized primarily by CYP1A2; therefore, coadministration of duloxetine with potent CYP1A2 inhibitors should be avoided. Duloxetine does not seem to be a clinically significant inhibitor or inducer of CYP1A2; therefore, dose adjustment of CYP1A2 substrates may not be necessary when they are coadministered with duloxetine.", "publicationTitle": "Clinical pharmacokinetics", "publisher": "", "place": "", "date": "2008", "volume": "47", "issue": "3", "section": "", "partNumber": "", "partTitle": "", "pages": "191-202", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Clin Pharmacokinet", "DOI": "", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/18307373", "accessDate": "2012-07-13T21:24:21Z", "PMID": "", "PMCID": "", "ISSN": "0312-5963", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 18307373", "tags": [ { "tag": "Administration, Oral", "type": 1 }, { "tag": "Adult", "type": 1 }, { "tag": "Area Under Curve", "type": 1 }, { "tag": "Biological Availability", "type": 1 }, { "tag": "Cross-Over Studies", "type": 1 }, { "tag": "Cytochrome P-450 CYP1A2", "type": 1 }, { "tag": "Drug Interactions", "type": 1 }, { "tag": "Female", "type": 1 }, { "tag": "Fluvoxamine", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Infusions, Intravenous", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Microsomes, Liver", "type": 1 }, { "tag": "Middle Aged", "type": 1 }, { "tag": "Serotonin Uptake Inhibitors", "type": 1 }, { "tag": "Sex Factors", "type": 1 }, { "tag": "Smoking", "type": 1 }, { "tag": "Theophylline", "type": 1 }, { "tag": "Thiophenes", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-07-13T21:24:21Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "8P8B5QQH", "version": 10, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/8P8B5QQH", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/8P8B5QQH", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Yu et al.", "parsedDate": "2001-04", "numChildren": 0 }, "data": { "key": "8P8B5QQH", "version": 10, "itemType": "journalArticle", "title": "Effect of omeprazole on the pharmacokinetics of moclobemide according to the genetic polymorphism of CYP2C19", "creators": [ { "creatorType": "author", "firstName": "K S", "lastName": "Yu" }, { "creatorType": "author", "firstName": "D S", "lastName": "Yim" }, { "creatorType": "author", "firstName": "J Y", "lastName": "Cho" }, { "creatorType": "author", "firstName": "S S", "lastName": "Park" }, { "creatorType": "author", "firstName": "J Y", "lastName": "Park" }, { "creatorType": "author", "firstName": "K H", "lastName": "Lee" }, { "creatorType": "author", "firstName": "I J", "lastName": "Jang" }, { "creatorType": "author", "firstName": "S Y", "lastName": "Yi" }, { "creatorType": "author", "firstName": "K S", "lastName": "Bae" }, { "creatorType": "author", "firstName": "S G", "lastName": "Shin" } ], "abstractNote": "BACKGROUND\n\nMoclobemide, an antidepressant with selective monoamine oxidase-A inhibitory action, is known to be metabolized by CYP2C19 and is also reported to be an inhibitor of CYP2C19, CYP2D6, and CYP1A2. To confirm the involvement of CYP2C19, we performed a pharmacokinetic interaction study.\n\n\nMETHODS\n\nThe effect of omeprazole on the pharmacokinetics of moclobemide was studied in 16 healthy volunteers. The volunteer group comprised 8 extensive metabolizers and 8 poor metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were randomly allocated into two sequence groups, and a single-blind, placebo-controlled, two-period crossover study was performed. In study I, a placebo was orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and 40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic study was performed. During study II, 40 mg of omeprazole was given each morning instead of placebo, and pharmacokinetic studies were performed on the first and eighth day with 300 mg of moclobemide coadministration.\n\n\nRESULTS\n\nThe inhibition of moclobemide metabolism was significant in extensive metabolizers even after a single dose of omeprazole. After daily administration of omeprazole for 1 week, the pharmacokinetic parameters of moclobemide and its metabolites in extensive metabolizers changed to values similar to those in poor metabolizers. In poor metabolizers, no remarkable changes in the pharmacokinetic parameters were observed.\n\n\nCONCLUSION\n\nOur results show that CYP2C19 is an important enzyme in the elimination of moclobemide and that it is extensively inhibited by omeprazole in extensive metabolizers, but not in poor metabolizers.", "publicationTitle": "Clinical pharmacology and therapeutics", "publisher": "", "place": "", "date": "Apr 2001", "volume": "69", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "266-273", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Clin. Pharmacol. Ther.", "DOI": "10.1067/mcp.2001.114231", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/11309556", "accessDate": "2012-07-13T20:52:50Z", "PMID": "", "PMCID": "", "ISSN": "0009-9236", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 11309556", "tags": [ { "tag": "Adult", "type": 1 }, { "tag": "Antidepressive Agents", "type": 1 }, { "tag": "Area Under Curve", "type": 1 }, { "tag": "Aryl Hydrocarbon Hydroxylases", "type": 1 }, { "tag": "Benzamides", "type": 1 }, { "tag": "Cross-Over Studies", "type": 1 }, { "tag": "Cytochrome P-450 Enzyme System", "type": 1 }, { "tag": "Drug Interactions", "type": 1 }, { "tag": "Enzyme Inhibitors", "type": 1 }, { "tag": "Genotype", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Mixed Function Oxygenases", "type": 1 }, { "tag": "Moclobemide", "type": 1 }, { "tag": "Morpholines", "type": 1 }, { "tag": "Omeprazole", "type": 1 }, { "tag": "Polymorphism, Genetic", "type": 1 }, { "tag": "Random Allocation", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-07-13T20:52:50Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "ER86E87S", "version": 10, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/ER86E87S", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/ER86E87S", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Bannister et al.", "parsedDate": "1989", "numChildren": 0 }, "data": { "key": "ER86E87S", "version": 10, "itemType": "journalArticle", "title": "Evaluation of the potential for interactions of paroxetine with diazepam, cimetidine, warfarin, and digoxin", "creators": [ { "creatorType": "author", "firstName": "S J", "lastName": "Bannister" }, { "creatorType": "author", "firstName": "V P", "lastName": "Houser" }, { "creatorType": "author", "firstName": "J D", "lastName": "Hulse" }, { "creatorType": "author", "firstName": "J C", "lastName": "Kisicki" }, { "creatorType": "author", "firstName": "J G", "lastName": "Rasmussen" } ], "abstractNote": "", "publicationTitle": "Acta psychiatrica Scandinavica. Supplementum", "publisher": "", "place": "", "date": "1989", "volume": "350", "issue": "", "section": "", "partNumber": "", "partTitle": "", "pages": "102-106", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Acta Psychiatr Scand Suppl", "DOI": "", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/2530759", "accessDate": "2012-07-03T18:34:02Z", "PMID": "", "PMCID": "", "ISSN": "0065-1591", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 2530759", "tags": [ { "tag": "Adult", "type": 1 }, { "tag": "Antidepressive Agents", "type": 1 }, { "tag": "Biological Availability", "type": 1 }, { "tag": "Cimetidine", "type": 1 }, { "tag": "Diazepam", "type": 1 }, { "tag": "Digoxin", "type": 1 }, { "tag": "Drug Interactions", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Paroxetine", "type": 1 }, { "tag": "Piperidines", "type": 1 }, { "tag": "Serotonin Antagonists", "type": 1 }, { "tag": "Warfarin", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-07-03T18:34:02Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "DE9QB3GC", "version": 10, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/DE9QB3GC", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/DE9QB3GC", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "de Leon et al.", "parsedDate": "2008-08", "numChildren": 0 }, "data": { "key": "DE9QB3GC", "version": 10, "itemType": "journalArticle", "title": "A preliminary attempt to personalize risperidone dosing using drug-drug interactions and genetics: part II", "creators": [ { "creatorType": "author", "firstName": "Jose", "lastName": "de Leon" }, { "creatorType": "author", "firstName": "Neil B", "lastName": "Sandson" }, { "creatorType": "author", "firstName": "Kelly L", "lastName": "Cozza" } ], "abstractNote": "", "publicationTitle": "Psychosomatics", "publisher": "", "place": "", "date": "2008 Jul-Aug", "volume": "49", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "347-361", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Psychosomatics", "DOI": "10.1176/appi.psy.49.4.347", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/18621942", "accessDate": "2012-06-19T18:21:57Z", "PMID": "", "PMCID": "", "ISSN": "0033-3182", "archive": "", "archiveLocation": "", "shortTitle": "A preliminary attempt to personalize risperidone dosing using drug-drug interactions and genetics", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 18621942", "tags": [ { "tag": "Alzheimer Disease", "type": 1 }, { "tag": "Child", "type": 1 }, { "tag": "Cytochrome P-450 CYP2D6", "type": 1 }, { "tag": "Cytochrome P-450 Enzyme System", "type": 1 }, { "tag": "Dose-Response Relationship, Drug", "type": 1 }, { "tag": "Drug Administration Schedule", "type": 1 }, { "tag": "Drug Interactions", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Intellectual Disability", "type": 1 }, { "tag": "Patient-Centered Care", "type": 1 }, { "tag": "Risperidone", "type": 1 }, { "tag": "Schizophrenia", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-06-19T18:21:57Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "WA4573X7", "version": 10, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/WA4573X7", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/WA4573X7", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "de Leon et al.", "parsedDate": "2008-06", "numChildren": 0 }, "data": { "key": "WA4573X7", "version": 10, "itemType": "journalArticle", "title": "A preliminary attempt to personalize risperidone dosing using drug-drug interactions and genetics: part I", "creators": [ { "creatorType": "author", "firstName": "Jose", "lastName": "de Leon" }, { "creatorType": "author", "firstName": "Neil B", "lastName": "Sandson" }, { "creatorType": "author", "firstName": "Kelly L", "lastName": "Cozza" } ], "abstractNote": "BACKGROUND\n\nPersonalized prescription is described even in lay journals, but there has been no attempt to propose personalizing dosing for any specific psychiatric drug.\n\n\nOBJECTIVE\n\nAny attempt to develop personalized dosing needs to be anchored in our understanding of the pharmacological response of each drug in each person's environment, particularly drug-drug interactions (DDIs) and how genetic make-up influences drug response.\n\n\nMETHOD\n\nRisperidone (R) is used as an example. R's pharmacologic response is reviewed in detail by focusing on our current knowledge of its pharmacodynamic and pharmacokinetic actions. The influences of the environment and genetics on these two actions are reviewed.\n\n\nRESULTS\n\nR's antipsychotic action is probably mainly explained by the blocking of dopamine receptors, particularly D(2) receptors. There are polymorphic variations of this gene (DRD(2)), but it is not clear that they have clinical relevance in predicting adverse drug reactions (ADRs) or antipsychotic response.\n\n\nCONCLUSION\n\nPrevious exposure to antipsychotics increases the need for higher R dosing, but the mechanism for this tolerance is not well understood. Other brain receptors, such as other dopamine, serotonin, and adrenergic receptors may explain some of these ADRs. Some polymorphic variations in these receptors have been described, but they cannot yet be used to personalize R dosing.", "publicationTitle": "Psychosomatics", "publisher": "", "place": "", "date": "2008 May-Jun", "volume": "49", "issue": "3", "section": "", "partNumber": "", "partTitle": "", "pages": "258-270", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Psychosomatics", "DOI": "10.1176/appi.psy.49.3.258", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/18448784", "accessDate": "2012-06-19T18:21:35Z", "PMID": "", "PMCID": "", "ISSN": "0033-3182", "archive": "", "archiveLocation": "", "shortTitle": "A preliminary attempt to personalize risperidone dosing using drug-drug interactions and genetics", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 18448784", "tags": [ { "tag": "Antipsychotic Agents", "type": 1 }, { "tag": "Binding Sites", "type": 1 }, { "tag": "Brain", "type": 1 }, { "tag": "Cytochrome P-450 CYP2D6", "type": 1 }, { "tag": "Drug Administration Schedule", "type": 1 }, { "tag": "Drug Interactions", "type": 1 }, { "tag": "Genotype", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Patient-Centered Care", "type": 1 }, { "tag": "Polymorphism, Genetic", "type": 1 }, { "tag": "Receptors, Adrenergic", "type": 1 }, { "tag": "Receptors, Dopamine D2", "type": 1 }, { "tag": "Receptors, Histamine", "type": 1 }, { "tag": "Receptors, Serotonin", "type": 1 }, { "tag": "Risperidone", "type": 1 }, { "tag": "Schizophrenia", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-06-19T18:21:35Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "MB64Z5XQ", "version": 9, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/MB64Z5XQ", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/MB64Z5XQ", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Tulner et al.", "parsedDate": "2008", "numChildren": 0 }, "data": { "key": "MB64Z5XQ", "version": 9, "itemType": "journalArticle", "title": "Drug-drug interactions in a geriatric outpatient cohort: prevalence and relevance.", "creators": [ { "creatorType": "author", "firstName": "L.R.", "lastName": "Tulner" }, { "creatorType": "author", "firstName": "S.V.", "lastName": "Frankfort" }, { "creatorType": "author", "firstName": "G.J.P.T.", "lastName": "Gijsen" }, { "creatorType": "author", "firstName": "J.P.C.M.", "lastName": "van Campen" }, { "creatorType": "author", "firstName": "C.H.W.", "lastName": "Koks" }, { "creatorType": "author", "firstName": "J.H.", "lastName": "Beijnen" } ], "abstractNote": "BACKGROUND The prevalence of drug-drug interactions (DDIs) in a geriatric population may be high because of polypharmacy. However, wide variance in the clinical relevance of these interactions has been shown. OBJECTIVES To explore whether adverse drug reactions (ADRs) as a result of DDIs can be identified by clinical evaluation, to describe the prevalence of ADRs and diminished drug effectiveness as a result of DDIs and to verify whether the top ten most frequent potential DDIs known to public pharmacies are of primary importance in geriatric outpatients in the Netherlands. METHOD All adverse events classified by the Naranjo algorithm as being a possible ADR and drug combinations resulting in diminished drug effectiveness were identified prospectively in 807 geriatric outpatients (mean age 81 years) at their first visit. The setting was a diagnostic day clinic. The Medication Appropriateness Index (MAI) and Beers criteria were used to evaluate drug use and identify possible DDIs. The ten most frequent potential interactions, according to a 1997 national database of public pharmacies ('Top Ten') in the Netherlands, and possible adverse events as a result of other interactions, were described. The effects of changes in medication regimen were recorded by checking the medical records. RESULTS In 300 patients (44.5% of the 674 patients taking more than one drug), 398 potential DDIs were identified. In 172 (25.5%) of patients taking more than one drug, drug combinations were identified that were responsible for at least one ADR or which possibly resulted in reduced effectiveness of therapy. Eighty-four of the 158 possible ADRs resulting from enhanced action of drugs forming combinations listed in the 'Top Ten' were seen in 73 patients. Only four DDIs resulting in less effective therapy that involved drug combinations in the 'Top Ten' were identified. Changes in drug regimens pertaining to possible interactions were proposed or put into effect in 111 of the 172 (65%) patients with possible DDIs. Sixty-one (55%) of these patients returned for follow-up. Of these, 49 (80%) were shown to have improved after changes were made to their medication regimen. CONCLUSION In this study, nearly half of the geriatric outpatients attending a diagnostic day clinic who were taking more than one drug were candidates for DDIs. One-quarter of these patients were found to have possible adverse events or diminished treatment effectiveness that may have been at least partly caused by these DDIs. These potential interactions can be identified through clinical evaluation. In the majority of patients (99 of 172) the potential interactions resulting in possible ADRs or diminished effectiveness were not present in the 'Top Ten' interactions described by a national database of public pharmacies, a finding that emphasizes that the particular characteristics of geriatric patients (e.g. frequent psychiatric co-morbidities) need to be considered when evaluating their drug use. At least 7% of all patients taking more than one drug, and 80% of those with possible drug interactions whose drug regimen was adjusted, benefited from changes made to their drug regimens.", "publicationTitle": "Drugs & Aging", "publisher": "", "place": "", "date": "(2008)", "volume": "25", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "343-355", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Drugs Aging", "DOI": "", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/18361544", "accessDate": "2011-06-07T21:57:05Z", "PMID": "", "PMCID": "", "ISSN": "1170-229X", "archive": "", "archiveLocation": "", "shortTitle": "Drug-drug interactions in a geriatric outpatient cohort", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 18361544", "tags": [ { "tag": "Aged", "type": 1 }, { "tag": "Aged, 80 and over", "type": 1 }, { "tag": "Cohort Studies", "type": 1 }, { "tag": "Drug Interactions", "type": 1 }, { "tag": "Female", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Outpatients", "type": 1 }, { "tag": "Pharmaceutical Preparations", "type": 1 }, { "tag": "Polypharmacy", "type": 1 }, { "tag": "Prevalence", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-10-02T18:12:13Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "BSWWGP9A", "version": 9, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/BSWWGP9A", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/BSWWGP9A", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Belleau et al.", "parsedDate": "2008-10", "numChildren": 0 }, "data": { "key": "BSWWGP9A", "version": 9, "itemType": "journalArticle", "title": "Bio2RDF: towards a mashup to build bioinformatics knowledge systems", "creators": [ { "creatorType": "author", "firstName": "François", "lastName": "Belleau" }, { "creatorType": "author", "firstName": "Marc-Alexandre", "lastName": "Nolin" }, { "creatorType": "author", "firstName": "Nicole", "lastName": "Tourigny" }, { "creatorType": "author", "firstName": "Philippe", "lastName": "Rigault" }, { "creatorType": "author", "firstName": "Jean", "lastName": "Morissette" } ], "abstractNote": "Presently, there are numerous bioinformatics databases available on different websites. Although RDF was proposed as a standard format for the web, these databases are still available in various formats. With the increasing popularity of the semantic web technologies and the ever growing number of databases in bioinformatics, there is a pressing need to develop mashup systems to help the process of bioinformatics knowledge integration. Bio2RDF is such a system, built from rdfizer programs written in JSP, the Sesame open source triplestore technology and an OWL ontology. With Bio2RDF, documents from public bioinformatics databases such as Kegg, PDB, MGI, HGNC and several of NCBI's databases can now be made available in RDF format through a unique URL in the form of http://bio2rdf.org/namespace:id. The Bio2RDF project has successfully applied the semantic web technology to publicly available databases by creating a knowledge space of RDF documents linked together with normalized URIs and sharing a common ontology. Bio2RDF is based on a three-step approach to build mashups of bioinformatics data. The present article details this new approach and illustrates the building of a mashup used to explore the implication of four transcription factor genes in Parkinson's disease. The Bio2RDF repository can be queried at http://bio2rdf.org.", "publicationTitle": "Journal of biomedical informatics", "publisher": "", "place": "", "date": "Oct 2008", "volume": "41", "issue": "5", "section": "", "partNumber": "", "partTitle": "", "pages": "706-716", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J Biomed Inform", "DOI": "10.1016/j.jbi.2008.03.004", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/18472304", "accessDate": "2012-09-18T17:00:12Z", "PMID": "", "PMCID": "", "ISSN": "1532-0480", "archive": "", "archiveLocation": "", "shortTitle": "Bio2RDF", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 18472304", "tags": [ { "tag": "Animals", "type": 1 }, { "tag": "Artificial intelligence", "type": 1 }, { "tag": "Computational Biology", "type": 1 }, { "tag": "Database Management Systems", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Information Dissemination", "type": 1 }, { "tag": "Information Storage and Retrieval", "type": 1 }, { "tag": "Internet", "type": 1 }, { "tag": "Parkinson Disease", "type": 1 }, { "tag": "Programming Languages", "type": 1 }, { "tag": "Semantics", "type": 1 }, { "tag": "Systems Integration", "type": 1 }, { "tag": "Terminology as Topic", "type": 1 }, { "tag": "Transcription Factors", "type": 1 }, { "tag": "Vocabulary, Controlled", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-10-02T17:55:58Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "RTCQPGPW", "version": 9, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/RTCQPGPW", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/RTCQPGPW", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Gurwitz et al.", "parsedDate": "2005", "numChildren": 0 }, "data": { "key": "RTCQPGPW", "version": 9, "itemType": "journalArticle", "title": "The incidence of adverse drug events in two large academic long-term care facilities.", "creators": [ { "creatorType": "author", "firstName": "J.H.", "lastName": "Gurwitz" }, { "creatorType": "author", "firstName": "T.S.", "lastName": "Field" }, { "creatorType": "author", "firstName": "J.", "lastName": "Judge" }, { "creatorType": "author", "firstName": "P.", "lastName": "Rochon" }, { "creatorType": "author", "firstName": "L.R.", "lastName": "Harrold" }, { "creatorType": "author", "firstName": "C.", "lastName": "Cadoret" }, { "creatorType": "author", "firstName": "M.", "lastName": "Lee" }, { "creatorType": "author", "firstName": "K.", "lastName": "White" }, { "creatorType": "author", "firstName": "J.", "lastName": "LaPrino" }, { "creatorType": "author", "firstName": "J.", "lastName": "Erramuspe-Mainard" }, { "creatorType": "author", "firstName": "M.", "lastName": "DeFlorio" }, { "creatorType": "author", "firstName": "L.", "lastName": "Gavendo" }, { "creatorType": "author", "firstName": "J.", "lastName": "Auger" }, { "creatorType": "author", "firstName": "D.W.", "lastName": "Bates" } ], "abstractNote": "PURPOSE To assess the incidence of and risk factors for adverse drug events in the long-term care setting. METHODS We performed a cohort study of all long-stay residents of two academic long-term care facilities over a period of up to 9 months during 2000 to 2001. We assessed the number of adverse drug events, the severity of events (classified as less serious, serious, life threatening, or fatal), and whether the events were preventable. A case-control study was nested within the prospective study to identify resident-level risk factors for the occurrence of adverse drug events. RESULTS There were 815 adverse drug events, of which 42% were judged preventable. The overall rate of adverse drug events was 9.8 per 100 resident-months, with a rate of 4.1 preventable adverse drug events per 100 resident-months. Errors associated with preventable events occurred most often at the stages of ordering and monitoring. Residents taking medications in several drug categories were at increased risk of a preventable adverse event. In multivariate analyses, the adjusted odds ratio was 3.4 (95% confidence interval [CI]: 2.0 to 5.9) for those taking antipsychotic agents, 2.8 (95% CI: 1.6 to 4.7) for those taking anticoagulants, 2.2 (95% CI: 1.2 to 4.0) for those taking diuretics, and 2.0 (95% CI: 1.1 to 3.7) for those taking antiepileptics. CONCLUSION Our findings reinforce the need for a special focus on the ordering and monitoring stages of pharmaceutical care for preventing adverse drug events in the long-term care setting. Patients taking antipsychotic agents, anticoagulants, diuretics, and antiepileptics are at increased risk.", "publicationTitle": "The American Journal of Medicine", "publisher": "", "place": "", "date": "(2005)", "volume": "118", "issue": "3", "section": "", "partNumber": "", "partTitle": "", "pages": "251-258", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Am. J. Med.", "DOI": "10.1016/j.amjmed.2004.09.018", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/15745723", "accessDate": "2011-06-07T21:57:05Z", "PMID": "", "PMCID": "", "ISSN": "0002-9343", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 15745723", "tags": [ { "tag": "Aged", "type": 1 }, { "tag": "Aged, 80 and over", "type": 1 }, { "tag": "Drug Interactions", "type": 1 }, { "tag": "Epidemiologic Methods", "type": 1 }, { "tag": "Female", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Long-Term Care", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Medication Errors", "type": 1 }, { "tag": "Nursing Homes", "type": 1 }, { "tag": "Pharmaceutical Preparations", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-10-02T18:12:13Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "52EKSA8J", "version": 9, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/52EKSA8J", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/52EKSA8J", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "McDonagh et al.", "parsedDate": "2011-12", "numChildren": 0 }, "data": { "key": "52EKSA8J", "version": 9, "itemType": "journalArticle", "title": "From pharmacogenomic knowledge acquisition to clinical applications: the PharmGKB as a clinical pharmacogenomic biomarker resource", "creators": [ { "creatorType": "author", "firstName": "Ellen M", "lastName": "McDonagh" }, { "creatorType": "author", "firstName": "Michelle", "lastName": "Whirl-Carrillo" }, { "creatorType": "author", "firstName": "Yael", "lastName": "Garten" }, { "creatorType": "author", "firstName": "Russ B", "lastName": "Altman" }, { "creatorType": "author", "firstName": "Teri E", "lastName": "Klein" } ], "abstractNote": "The mission of the Pharmacogenomics Knowledge Base (PharmGKB; www.pharmgkb.org ) is to collect, encode and disseminate knowledge about the impact of human genetic variations on drug responses. It is an important worldwide resource of clinical pharmacogenomic biomarkers available to all. The PharmGKB website has evolved to highlight our knowledge curation and aggregation over our previous emphasis on collecting primary data. This review summarizes the methods we use to drive this expanded scope of 'Knowledge Acquisition to Clinical Applications', the new features available on our website and our future goals.", "publicationTitle": "Biomarkers in medicine", "publisher": "", "place": "", "date": "Dec 2011", "volume": "5", "issue": "6", "section": "", "partNumber": "", "partTitle": "", "pages": "795-806", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Biomark Med", "DOI": "10.2217/bmm.11.94", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/22103613", "accessDate": "2012-09-14T19:38:16Z", "PMID": "", "PMCID": "", "ISSN": "1752-0371", "archive": "", "archiveLocation": "", "shortTitle": "From pharmacogenomic knowledge acquisition to clinical applications", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 22103613", "tags": [ { "tag": "Biological Markers", "type": 1 }, { "tag": "Databases, Factual", "type": 1 }, { "tag": "Genetic Variation", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Internet", "type": 1 }, { "tag": "Knowledge Bases", "type": 1 }, { "tag": "Pharmacogenetics", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-10-02T17:55:58Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "T5UPUTZ6", "version": 9, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/T5UPUTZ6", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/T5UPUTZ6", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Samsa et al.", "parsedDate": "1994-08", "numChildren": 0 }, "data": { "key": "T5UPUTZ6", "version": 9, "itemType": "journalArticle", "title": "A summated score for the medication appropriateness index: development and assessment of clinimetric properties including content validity", "creators": [ { "creatorType": "author", "firstName": "G P", "lastName": "Samsa" }, { "creatorType": "author", "firstName": "J T", "lastName": "Hanlon" }, { "creatorType": "author", "firstName": "K E", "lastName": "Schmader" }, { "creatorType": "author", "firstName": "M", "lastName": "Weinberger" }, { "creatorType": "author", "firstName": "E C", "lastName": "Clipp" }, { "creatorType": "author", "firstName": "K M", "lastName": "Uttech" }, { "creatorType": "author", "firstName": "I K", "lastName": "Lewis" }, { "creatorType": "author", "firstName": "P B", "lastName": "Landsman" }, { "creatorType": "author", "firstName": "H J", "lastName": "Cohen" } ], "abstractNote": "Inappropriate medication prescribing is an important problem in the elderly, but is difficult to measure. As part of a randomized controlled trial to evaluate the effectiveness of a pharmacist intervention among elderly veterans using many medications, we developed the Medication Appropriateness Index (MAI), which uses implicit criteria to measure elements of appropriate prescribing. This paper describes the development and validation of a weighting scheme used to produce a single summated MAI score per medication. Using this weighting scheme, two clinical pharmacists rated 105 medications prescribed to 10 elderly veterans from a general medicine clinic. The summated score demonstrated acceptable reliability (intraclass correlation co-efficient = 0.74). In addition, the summated MAI adequately reflected the putative heterogeneity in prescribing appropriateness among 1644 medications prescribed to 208 elderly veterans in the same general medicine clinic. These data support the content validity of the summated MAI. The MAI appears to be a relatively reliable, valid measure of prescribing appropriateness and may be useful for research studies, quality improvement programs, and patient care.", "publicationTitle": "Journal of clinical epidemiology", "publisher": "", "place": "", "date": "Aug 1994", "volume": "47", "issue": "8", "section": "", "partNumber": "", "partTitle": "", "pages": "891-896", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J Clin Epidemiol", "DOI": "", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/7730892", "accessDate": "2012-07-14T14:38:27Z", "PMID": "", "PMCID": "", "ISSN": "0895-4356", "archive": "", "archiveLocation": "", "shortTitle": "A summated score for the medication appropriateness index", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 7730892", "tags": [ { "tag": "Aged", "type": 1 }, { "tag": "Drug Utilization Review", "type": 1 }, { "tag": "Female", "type": 1 }, { "tag": "Health Services for the Aged", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Pharmaceutical Services", "type": 1 }, { "tag": "Reproducibility of Results", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-07-14T14:38:27Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "XHZQSXXM", "version": 9, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/XHZQSXXM", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/XHZQSXXM", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Yasui-Furukori et al.", "parsedDate": "2007-01", "numChildren": 0 }, "data": { "key": "XHZQSXXM", "version": 9, "itemType": "journalArticle", "title": "Terbinafine increases the plasma concentration of paroxetine after a single oral administration of paroxetine in healthy subjects", "creators": [ { "creatorType": "author", "firstName": "Norio", "lastName": "Yasui-Furukori" }, { "creatorType": "author", "firstName": "Manabu", "lastName": "Saito" }, { "creatorType": "author", "firstName": "Yoshimasa", "lastName": "Inoue" }, { "creatorType": "author", "firstName": "Takenori", "lastName": "Niioka" }, { "creatorType": "author", "firstName": "Yasushi", "lastName": "Sato" }, { "creatorType": "author", "firstName": "Shoko", "lastName": "Tsuchimine" }, { "creatorType": "author", "firstName": "Sunao", "lastName": "Kaneko" } ], "abstractNote": "OBJECTIVE\n\nParoxetine is believed to be a substrate of CYP2D6. However, no information was available indicating drug interaction between paroxetine and inhibitors of CYP2D6. The aim of this study was to examine the effects of terbinafine, a potent inhibitor of CYP2D6, on pharmacokinetics of paroxetine.\n\n\nMETHODS\n\nTwo 6-day courses of either a daily 150-mg of terbinafine or a placebo, with at least a 4-week washout period, were conducted. Twelve volunteers took a single oral 20-mg dose of paroxetine on day 6 of both courses. Plasma concentrations of paroxetine were monitored up to 48 h after dosing.\n\n\nRESULTS\n\nCompared with the placebo, terbinafine treatment significantly increased the peak plasma concentration (C(max)) of paroxetine, by 1.9-fold (6.4 +/- 2.4 versus 12.1 +/- 2.9 ng/ml, p < 0.001), and the area under the plasma concentration-time curve from zero to 48 h [AUC (0-48)] of paroxetine by 2.5-fold (127 +/- 67 vs 318 +/- 102 ng/ml, p < 0.001). Elimination half-life differed significantly (15.3 +/- 2.4 vs 22.7 +/- 8.8 h, p < 0.05), although the magnitude of alteration (1.4-fold) was smaller than C(max )or AUC.\n\n\nCONCLUSION\n\nThe present study demonstrated that the metabolism of paroxetine after a single oral dose was inhibited by terbinafine, suggesting that inhibition of CYP2D6 activity may lead to a change in the pharmacokinetics of paroxetine. However, further study is required to confirm this phenomenon at steady state.", "publicationTitle": "European journal of clinical pharmacology", "publisher": "", "place": "", "date": "Jan 2007", "volume": "63", "issue": "1", "section": "", "partNumber": "", "partTitle": "", "pages": "51-56", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Eur. J. Clin. Pharmacol.", "DOI": "10.1007/s00228-006-0217-9", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/17124578", "accessDate": "2012-07-03T18:34:28Z", "PMID": "", "PMCID": "", "ISSN": "0031-6970", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 17124578", "tags": [ { "tag": "Administration, Oral", "type": 1 }, { "tag": "Adult", "type": 1 }, { "tag": "Antidepressive Agents, Second-Generation", "type": 1 }, { "tag": "Antifungal Agents", "type": 1 }, { "tag": "Area Under Curve", "type": 1 }, { "tag": "Biological Availability", "type": 1 }, { "tag": "Chromatography, High Pressure Liquid", "type": 1 }, { "tag": "Cross-Over Studies", "type": 1 }, { "tag": "Cytochrome P-450 CYP2D6", "type": 1 }, { "tag": "Drug Synergism", "type": 1 }, { "tag": "Female", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Naphthalenes", "type": 1 }, { "tag": "Paroxetine", "type": 1 }, { "tag": "Serotonin Uptake Inhibitors", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-07-03T18:34:28Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "E44THZGP", "version": 9, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/E44THZGP", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/E44THZGP", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Turpeinen et al.", "parsedDate": "2005-06", "numChildren": 0 }, "data": { "key": "E44THZGP", "version": 9, "itemType": "journalArticle", "title": "Effect of clopidogrel and ticlopidine on cytochrome P450 2B6 activity as measured by bupropion hydroxylation", "creators": [ { "creatorType": "author", "firstName": "Miia", "lastName": "Turpeinen" }, { "creatorType": "author", "firstName": "Ari", "lastName": "Tolonen" }, { "creatorType": "author", "firstName": "Jouko", "lastName": "Uusitalo" }, { "creatorType": "author", "firstName": "Jorma", "lastName": "Jalonen" }, { "creatorType": "author", "firstName": "Olavi", "lastName": "Pelkonen" }, { "creatorType": "author", "firstName": "Kari", "lastName": "Laine" } ], "abstractNote": "OBJECTIVE\n\nOur objective was to study the effect of the antiplatelet agents clopidogrel and ticlopidine on bupropion (INN, amfebutamone) hydroxylation, a probe reaction for cytochrome P450 (CYP) 2B6 activity.\n\n\nMETHODS\n\nTwelve healthy male volunteers took a single 150-mg oral dose of bupropion either alone or after pretreatment with 75 mg clopidogrel once daily or 250 mg ticlopidine twice daily for 4 days. On day 4, a single 150-mg oral dose of bupropion was administered. Plasma concentrations of bupropion and its CYP2B6-catalyzed metabolite, hydroxybupropion, were measured for up to 72 hours.\n\n\nRESULTS\n\nThe mean area under the plasma concentration-time curve (AUC) of hydroxybupropion calculated from time 0 to infinity was reduced by 52% ( P = .001; 95% confidence interval [CI], 39% to 66%) by clopidogrel and by 84% ( P < .0001; 95% CI, 73% to 94%) by ticlopidine. Clopidogrel reduced the AUC ratio of hydroxybupropion over bupropion by 68% ( P = .002; 95% CI, 58% to 77%) and ticlopidine by 90% ( P = .001; 95% CI, 85% to 96%). The AUC of bupropion was increased by 60% ( P = .02; 95% CI, 21% to 98%) and by 85% ( P < .0001; 95% CI, 48% to 85%) with clopidogrel and ticlopidine, respectively.\n\n\nCONCLUSIONS\n\nBoth clopidogrel and ticlopidine significantly inhibited the CYP2B6-catalyzed bupropion hydroxylation. Patients receiving either clopidogrel or ticlopidine are likely to require dose adjustments when treated with drugs primarily metabolized by CYP2B6.", "publicationTitle": "Clinical Pharmacology and Therapeutics", "publisher": "", "place": "", "date": "Jun 2005", "volume": "77", "issue": "6", "section": "", "partNumber": "", "partTitle": "", "pages": "553-559", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Clin Pharmacol Ther", "DOI": "10.1016/j.clpt.2005.02.010", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/15961986", "accessDate": "2011-09-15T18:03:28Z", "PMID": "", "PMCID": "", "ISSN": "0009-9236", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 15961986", "tags": [ { "tag": "Adult", "type": 1 }, { "tag": "Aryl Hydrocarbon Hydroxylases", "type": 1 }, { "tag": "Bupropion", "type": 1 }, { "tag": "Cross-Over Studies", "type": 1 }, { "tag": "Dopamine Uptake Inhibitors", "type": 1 }, { "tag": "Dose-Response Relationship, Drug", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Hydroxylation", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Oxidoreductases, N-Demethylating", "type": 1 }, { "tag": "Platelet Aggregation Inhibitors", "type": 1 }, { "tag": "Ticlopidine", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-07-03T18:04:04Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "54V3J62F", "version": 9, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/54V3J62F", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/54V3J62F", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "de Leon et al.", "parsedDate": "2006-02", "numChildren": 0 }, "data": { "key": "54V3J62F", "version": 9, "itemType": "journalArticle", "title": "Clinical guidelines for psychiatrists for the use of pharmacogenetic testing for CYP450 2D6 and CYP450 2C19", "creators": [ { "creatorType": "author", "firstName": "Jose", "lastName": "de Leon" }, { "creatorType": "author", "firstName": "Scott C", "lastName": "Armstrong" }, { "creatorType": "author", "firstName": "Kelly L", "lastName": "Cozza" } ], "abstractNote": "Pharmacogenetics has arrived in clinical psychiatric practice with the FDA approval of the AmpliChip CYP450 Test that genotypes for two cytochrome P450 2D6 (CYP2D6) and 2C19 (CYP2C19) genes. Other pharmacogenetic tests, including those focused on pharmacodynamic genes, are far from ready for clinical application. CYP2D6 is important for the metabolism of many antidepressants and antipsychotics, and CY2C19 is important for some antidepressant metabolism. Poor metabolizers (PMs), lacking the enzyme, account for up to 7% of Caucasians for CYP2D6 and up to 25% of East Asians for CYP2C19. Patients having three or more active CYP2D6 alleles (up to 29% in North Africa and the Middle East), are called CYP2D6 ultra-rapid metabolizers (UMs). CYP2D6 phenotypes (particularly PMs) are probably important in patients taking tricyclic antidepressants (TCAs), venlafaxine, typical antipsychotics, and risperidone. The CYP2C19 PM phenotype is probably important in patients taking TCAs and perhaps citalopram, escitalopram, and sertraline. On the basis of the literature and the authors' clinical experience, the authors provide provisional recommendations for identifying and treating CYP2D6 PMs, CYP2C19 PMs, and CYP2D6 UMs. The next few years will determine whether CYP2D6 genotyping is beneficial for patients taking the new drugs aripiprazole, duloxetine, and atomoxetine. Practical recommendations for dealing with laboratories offering CYP2D6 and CYP2C29 genotyping are provided.", "publicationTitle": "Psychosomatics", "publisher": "", "place": "", "date": "2006 Jan-Feb", "volume": "47", "issue": "1", "section": "", "partNumber": "", "partTitle": "", "pages": "75-85", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Psychosomatics", "DOI": "10.1176/appi.psy.47.1.75", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/16384813", "accessDate": "2012-06-19T18:17:32Z", "PMID": "", "PMCID": "", "ISSN": "0033-3182", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 16384813", "tags": [ { "tag": "Aryl Hydrocarbon Hydroxylases", "type": 1 }, { "tag": "Cytochrome P-450 CYP2D6", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Mental Disorders", "type": 1 }, { "tag": "Mixed Function Oxygenases", "type": 1 }, { "tag": "Pharmacogenetics", "type": 1 }, { "tag": "Practice Guidelines as Topic", "type": 1 }, { "tag": "Psychiatry", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-06-19T18:17:32Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "69I45KXD", "version": 9, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/69I45KXD", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/69I45KXD", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "de Leon et al.", "parsedDate": "2009-01", "numChildren": 0 }, "data": { "key": "69I45KXD", "version": 9, "itemType": "journalArticle", "title": "DNA microarray technology in the clinical environment: the AmpliChip CYP450 test for CYP2D6 and CYP2C19 genotyping", "creators": [ { "creatorType": "author", "firstName": "Jose", "lastName": "de Leon" }, { "creatorType": "author", "firstName": "Margaret T", "lastName": "Susce" }, { "creatorType": "author", "firstName": "Maria", "lastName": "Johnson" }, { "creatorType": "author", "firstName": "Mike", "lastName": "Hardin" }, { "creatorType": "author", "firstName": "Lorraine", "lastName": "Maw" }, { "creatorType": "author", "firstName": "Alison", "lastName": "Shao" }, { "creatorType": "author", "firstName": "Antonette C P", "lastName": "Allen" }, { "creatorType": "author", "firstName": "Francis A", "lastName": "Chiafari" }, { "creatorType": "author", "firstName": "Grantland", "lastName": "Hillman" }, { "creatorType": "author", "firstName": "D Michele", "lastName": "Nikoloff" } ], "abstractNote": "INTRODUCTION\n\nAn important technological advance in genetic testing is the DNA microarray, which allows for the simultaneous testing of thousands of DNA sequences. The AmpliChip CYP450 Test employs this microarray technology for cytochrome P450 (CYP) 2D6 and CYP2C19 genotyping. Isoenzymes encoded by these genes are responsible for the metabolism of many widely prescribed drugs. The objectives of this study were to identify CYP2D6 and CYP2C19 alleles and phenotypes in a psychiatric patient population in Kentucky, and to describe practical issues associated with DNA microarray technology.\n\n\nMETHODS\n\nA total of 4,532 psychiatric patients were recruited from three state hospitals in Kentucky. Whole blood, buccal swabs, or saliva samples were genotyped with the AmpliChip CYP450 Test to derive a predicted phenotype.\n\n\nRESULTS\n\nIn this cohort, the overall prevalence of CYP2D6 poor metabolizers was 7.6% (95% CI 7%, 8.3%), 8.2% in the Caucasians (95% CI 7.4%, 9.%) and 1.8% in the African Americans (95% CI 0.9%, 3.5%). The overall prevalence of CYP2D6 ultrarapid metabolizers was 1.5% (95% CI 1.2%, 1.9%), 1.5% in the Caucasians (95% CI 1.1%, 1.9%) and 2.0% in the African Americans (95% CI 1.1%, 3.7%). The overall prevalence of CYP2C19 poor metabolizers was 2.0% (95% CI 1.8%, 2.7%), 2.2% in Caucasians (95% CI 1.6%, 2.5%) and 4.0% in African Americans (95% CI 2.6%, 6.1%).\n\n\nCONCLUSION\n\nWe also propose a numeric system for expression of CYP2D6 and CYP2C19 enzyme activity to aid clinicians in determining treatment strategy for patients receiving therapeutics that are metabolized by the CYP2D6 or CYP2C19 gene products.", "publicationTitle": "CNS spectrums", "publisher": "", "place": "", "date": "Jan 2009", "volume": "14", "issue": "1", "section": "", "partNumber": "", "partTitle": "", "pages": "19-34", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "CNS Spectr", "DOI": "", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/19169185", "accessDate": "2012-06-19T18:13:57Z", "PMID": "", "PMCID": "", "ISSN": "1092-8529", "archive": "", "archiveLocation": "", "shortTitle": "DNA microarray technology in the clinical environment", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 19169185", "tags": [ { "tag": "Aryl Hydrocarbon Hydroxylases", "type": 1 }, { "tag": "Cohort Studies", "type": 1 }, { "tag": "Cytochrome P-450 CYP2D6", "type": 1 }, { "tag": "Cytochrome P-450 Enzyme System", "type": 1 }, { "tag": "Gene Frequency", "type": 1 }, { "tag": "Genotype", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Kentucky", "type": 1 }, { "tag": "Mental Disorders", "type": 1 }, { "tag": "Oligonucleotide Array Sequence Analysis", "type": 1 }, { "tag": "Phenotype", "type": 1 }, { "tag": "Prevalence", "type": 1 }, { "tag": "Psychiatry", "type": 1 }, { "tag": "Review Literature as Topic", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-06-19T18:13:57Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "DHKNEE2R", "version": 9, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/DHKNEE2R", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/DHKNEE2R", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Preskorn", "parsedDate": "2010-01", "numChildren": 0 }, "data": { "key": "DHKNEE2R", "version": 9, "itemType": "journalArticle", "title": "Understanding outliers on the usual dose-response curve: venlafaxine as a way to phenotype patients in terms of their CYP 2D6 status and why it matters", "creators": [ { "creatorType": "author", "firstName": "Sheldon H", "lastName": "Preskorn" } ], "abstractNote": "Venlafaxine is a model substrate for the drug metabolizing cytochrome P450 (CYP) enzyme 2D6. The desvenlafaxine/venlafaxine ratio, either after a single dose or at steady state, can be used to determine whether a patient is functionally (i.e., phenotypically) a CYP 2D6 extensive or poor metabolizer (EM or PM). In turn, CYP 2D6 EM and PM status is important in determining the efficacy of venlafaxine as an antidepressant. Based on a secondary analysis of four of the venlafaxine registration trials, venlafaxine was effective in patients who were CYP 2D6 EMs versus a parallel placebo-treated control group, whereas it was not effective in patients who were CYP 2D6 PMs. Thus, venlafaxine is a useful example of how drugs can be used to quantify differences in drug metabolizing capacity among patients and how such differences can in turn affect the efficacy of a drug (i.e., make a patient an outlier on the usual dose-response curve).", "publicationTitle": "Journal of psychiatric practice", "publisher": "", "place": "", "date": "Jan 2010", "volume": "16", "issue": "1", "section": "", "partNumber": "", "partTitle": "", "pages": "46-49", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J Psychiatr Pract", "DOI": "10.1097/01.pra.0000367777.96012.83", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/20098230", "accessDate": "2012-06-19T14:26:57Z", "PMID": "", "PMCID": "", "ISSN": "1538-1145", "archive": "", "archiveLocation": "", "shortTitle": "Understanding outliers on the usual dose-response curve", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 20098230", "tags": [ { "tag": "Antidepressive Agents, Second-Generation", "type": 1 }, { "tag": "Cyclohexanols", "type": 1 }, { "tag": "Cytochrome P-450 CYP2D6", "type": 1 }, { "tag": "Dose-Response Relationship, Drug", "type": 1 }, { "tag": "Genetic Variation", "type": 1 }, { "tag": "Genotype", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Phenotype", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-06-19T14:26:57Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "AMGMV3WR", "version": 8, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/AMGMV3WR", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/AMGMV3WR", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Hamilton et al.", "parsedDate": "1998", "numChildren": 0 }, "data": { "key": "AMGMV3WR", "version": 8, "itemType": "journalArticle", "title": "Frequency of hospitalization after exposure to known drug-drug interactions in a Medicaid population.", "creators": [ { "creatorType": "author", "firstName": "R.A.", "lastName": "Hamilton" }, { "creatorType": "author", "firstName": "L.L.", "lastName": "Briceland" }, { "creatorType": "author", "firstName": "M.H.", "lastName": "Andritz" } ], "abstractNote": "A matched-pair case-control analysis of Medicaid claims was performed to determine the risks of hospitalization associated with drug-drug interactions. Patients were hospitalized and controls were not. They were randomly matched based on contemporaneous eligibility for Medicaid benefits. Odds ratios for hospitalization in patients exposed to known drug-drug interactions were compared with those in patients exposed to one of the interacting agents. When confidence intervals did not overlap, the odds ratio was considered to be significantly increased. Odds ratios were significantly increased for many interacting drug pairs, and were associated with commonly recognized interactions as well as less widely recognized ones. Cimetidine interactions achieved significance only with theophylline. In the Medicaid population, exposure to a number of drug-drug interactions was associated with a significantly increased risk of hospitalization.", "publicationTitle": "Pharmacotherapy", "publisher": "", "place": "", "date": "(1998)", "volume": "18", "issue": "5", "section": "", "partNumber": "", "partTitle": "", "pages": "1112-1120", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Pharmacotherapy", "DOI": "", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/9758323", "accessDate": "2011-09-09T13:51:41Z", "PMID": "", "PMCID": "", "ISSN": "0277-0008", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 9758323", "tags": [ { "tag": "Adolescent", "type": 1 }, { "tag": "Adult", "type": 1 }, { "tag": "Aged", "type": 1 }, { "tag": "Aged, 80 and over", "type": 1 }, { "tag": "Case-Control Studies", "type": 1 }, { "tag": "Child", "type": 1 }, { "tag": "Child, Preschool", "type": 1 }, { "tag": "Drug Interactions", "type": 1 }, { "tag": "Female", "type": 1 }, { "tag": "Hospitalization", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Iatrogenic Disease", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Medicaid", "type": 1 }, { "tag": "Middle Aged", "type": 1 }, { "tag": "New York", "type": 1 }, { "tag": "Pharmaceutical Preparations", "type": 1 }, { "tag": "United States", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-10-02T18:13:20Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "7T24TVJT", "version": 8, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/7T24TVJT", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/7T24TVJT", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Juurlink et al.", "parsedDate": "2003", "numChildren": 0 }, "data": { "key": "7T24TVJT", "version": 8, "itemType": "journalArticle", "title": "Drug-drug interactions among elderly patients hospitalized for drug toxicity.", "creators": [ { "creatorType": "author", "firstName": "D.N.", "lastName": "Juurlink" }, { "creatorType": "author", "firstName": "M.", "lastName": "Mamdani" }, { "creatorType": "author", "firstName": "A.", "lastName": "Kopp" }, { "creatorType": "author", "firstName": "A.", "lastName": "Laupacis" }, { "creatorType": "author", "firstName": "D.A.", "lastName": "Redelmeier" } ], "abstractNote": "CONTEXT Drug-drug interactions are a preventable cause of morbidity and mortality, yet their consequences in the community are not well characterized. OBJECTIVE To determine whether elderly patients admitted to hospital with specific drug toxicities were likely to have been prescribed an interacting drug in the week prior to admission. DESIGN Three population-based, nested case-control studies. SETTING Ontario, Canada, from January 1, 1994, to December 31, 2000. PATIENTS All Ontario residents aged 66 years or older treated with glyburide, digoxin, or an angiotensin-converting enzyme (ACE) inhibitor. Case patients were those admitted to hospital for drug-related toxicity. Prescription records of cases were compared with those of controls (matched on age, sex, use of the same medication, and presence or absence of renal disease) for receipt of interacting medications (co-trimoxazole with glyburide, clarithromycin with digoxin, and potassium-sparing diuretics with ACE inhibitors). MAIN OUTCOME MEASURE Odds ratio for association between hospital admission for drug toxicity (hypoglycemia, digoxin toxicity, or hyperkalemia, respectively) and use of an interacting medication in the preceding week, adjusted for diagnoses, receipt of other medications, the number of prescription drugs, and the number of hospital admissions in the year preceding the index date. RESULTS During the 7-year study period, 909 elderly patients receiving glyburide were admitted with a diagnosis of hypoglycemia. In the primary analysis, those patients admitted for hypoglycemia were more than 6 times as likely to have been treated with co-trimoxazole in the previous week (adjusted odds ratio, 6.6; 95% confidence interval, 4.5-9.7). Patients admitted with digoxin toxicity (n = 1051) were about 12 times more likely to have been treated with clarithromycin (adjusted odds ratio, 11.7; 95% confidence interval, 7.5-18.2) in the previous week, and patients treated with ACE inhibitors admitted with a diagnosis of hyperkalemia (n = 523) were about 20 times more likely to have been treated with a potassium-sparing diuretic (adjusted odds ratio, 20.3; 95% confidence interval, 13.4-30.7) in the previous week. No increased risk of drug toxicity was found for drugs with similar indications but no known interactions (amoxicillin, cefuroxime, and indapamide, respectively). CONCLUSIONS Many hospital admissions of elderly patients for drug toxicity occur after administration of a drug known to cause drug-drug interactions. Many of these interactions could have been avoided.", "publicationTitle": "JAMA: The Journal of the American Medical Association", "publisher": "", "place": "", "date": "(2003)", "volume": "289", "issue": "13", "section": "", "partNumber": "", "partTitle": "", "pages": "1652-1658", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "JAMA", "DOI": "10.1001/jama.289.13.1652", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/12672733", "accessDate": "2011-06-07T21:57:05Z", "PMID": "", "PMCID": "", "ISSN": "0098-7484", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 12672733", "tags": [ { "tag": "Aged", "type": 1 }, { "tag": "Angiotensin-Converting Enzyme Inhibitors", "type": 1 }, { "tag": "Anti-Asthmatic Agents", "type": 1 }, { "tag": "Anti-Infective Agents", "type": 1 }, { "tag": "Antihypertensive Agents", "type": 1 }, { "tag": "Case-Control Studies", "type": 1 }, { "tag": "Clarithromycin", "type": 1 }, { "tag": "Digoxin", "type": 1 }, { "tag": "Diuretics", "type": 1 }, { "tag": "Drug Interactions", "type": 1 }, { "tag": "Drug Toxicity", "type": 1 }, { "tag": "Female", "type": 1 }, { "tag": "Glyburide", "type": 1 }, { "tag": "Hospitalization", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Hyperkalemia", "type": 1 }, { "tag": "Hypoglycemia", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Ontario", "type": 1 }, { "tag": "Trimethoprim-Sulfamethoxazole Combination", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-10-02T18:12:13Z", "dateModified": "2012-10-08T17:23:23Z" } }, { "key": "CVFCHZ47", "version": 7, "library": { "type": "group", "id": 81210, "name": "pharmacogenomics-and-drug-drug-interactions", "links": { "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/81210/items/CVFCHZ47", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/pharmacogenomics-and-drug-drug-interactions/items/CVFCHZ47", "type": "text/html" } }, "meta": { "createdByUser": { "id": 8771, "username": "boycer", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/boycer", "type": "text/html" } } }, "creatorSummary": "Zint et al.", "parsedDate": "2010-12", "numChildren": 0 }, "data": { "key": "CVFCHZ47", "version": 7, "itemType": "journalArticle", "title": "Impact of drug interactions, dosage, and duration of therapy on the risk of hip fracture associated with benzodiazepine use in older adults", "creators": [ { "creatorType": "author", "firstName": "Kristina", "lastName": "Zint" }, { "creatorType": "author", "firstName": "Walter E", "lastName": "Haefeli" }, { "creatorType": "author", "firstName": "Robert J", "lastName": "Glynn" }, { "creatorType": "author", "firstName": "Helen", "lastName": "Mogun" }, { "creatorType": "author", "firstName": "Jerry", "lastName": "Avorn" }, { "creatorType": "author", "firstName": "Til", "lastName": "Stürmer" } ], "abstractNote": "PURPOSE\n\nTo determine how concomitant use of potentially interacting drugs, drug dosage, and duration of therapy modify the risk of hip fracture associated with use of benzodiazepines and benzodiazepine-related drugs (BDZ) in older adults.\n\n\nMETHODS\n\nA nested case-control study was conducted in Medicare patients 65 years or older, enrolled in the Pennsylvania drug assistance program (PACE) between 1994 and 2005. We included 17,198 patients with a hip fracture leading to hospitalization and 85,990 controls matched on hospitalization (index date). BDZ and interacting drug use within 2 weeks preceding the index date was determined using information on date of drug dispensing, days supplied, quantity dispensed, and strength. Date of the first BDZ prescription within the year preceding the index date was used as surrogate for duration of therapy.\n\n\nRESULTS\n\nWhile the adjusted relative risk (RR) for overall BDZ use and hip fracture was 1.2 (95% confidence interval 1.1, 1.2), the RRs for concomitant use of alprazolam, lorazepam, and zolpidem and their interacting drugs were 1.5 (1.3, 1.7), 1.9 (1.7, 2.2), and 1.7 (1.4, 2.0), and 2.1 (1.5, 2.8) for BDZ use initiated within 14 days preceding the index date. RR increased with increasing BDZ dose and was highest for defined daily BDZ doses >1 [RR: 1.3 (1.2, 1.5)].\n\n\nCONCLUSIONS\n\nBDZ associated hip fracture risk increases with concomitant use of interacting drugs, higher doses, and is highest at initiation. Clinicians should avoid concomitant use of BDZ and interacting drugs, because their impact on hip fracture risk is at least additive.", "publicationTitle": "Pharmacoepidemiology and Drug Safety", "publisher": "", "place": "", "date": "Dec 2010", "volume": "19", "issue": "12", "section": "", "partNumber": "", "partTitle": "", "pages": "1248-1255", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Pharmacoepidemiol Drug Saf", "DOI": "10.1002/pds.2031", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pubmed/20931664", "accessDate": "2011-09-14T17:03:43Z", "PMID": "", "PMCID": "", "ISSN": "1099-1557", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 20931664", "tags": [ { "tag": "Aged", "type": 1 }, { "tag": "Aged, 80 and over", "type": 1 }, { "tag": "Benzodiazepines", "type": 1 }, { "tag": "Case-Control Studies", "type": 1 }, { "tag": "Dose-Response Relationship, Drug", "type": 1 }, { "tag": "Drug Interactions", "type": 1 }, { "tag": "Female", "type": 1 }, { "tag": "Hip Fractures", "type": 1 }, { "tag": "Hospitalization", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Medicare", "type": 1 }, { "tag": "Pennsylvania", "type": 1 }, { "tag": "Risk", "type": 1 }, { "tag": "Time Factors", "type": 1 }, { "tag": "United States", "type": 1 } ], "collections": [], "relations": {}, "dateAdded": "2012-10-02T18:15:44Z", "dateModified": "2012-10-08T17:23:23Z" } } ]