{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T06:56:07Z","timestamp":1789368967485,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,3,7]],"date-time":"2013-03-07T00:00:00Z","timestamp":1362614400000},"content-version":"vor","delay-in-days":2226,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:p>In vitro\u2013in vivo extrapolation of clearance, embedded in a clinical trial simulation, was used to investigate differences in the pharmacokinetics and pharmacodynamics of dextromethorphan between CYP2D6 poor and extensive metabolizer phenotypes. Information on the genetic variation of CYP2D6, as well as the in vitro metabolism and pharmacodynamics of dextromethorphan and its active metabolite dextrorphan, was integrated to assess the power of studies to detect differences between phenotypes. Whereas 6 subjects of each phenotype were adequate to achieve 80% power in showing pharmacokinetic differences, the power required to detect a difference in antitussive response was less than 80% with 500 subjects in each study arm. Combining in vitro\u2013in vivo extrapolation with a clinical trial simulation is useful in assessing different elements of study design and could be used a priori to avoid inconclusive pharmacogenetic studies.<\/jats:p>","DOI":"10.1177\/0091270006294279","type":"journal-article","created":{"date-parts":[[2007,1,23]],"date-time":"2007-01-23T20:39:06Z","timestamp":1169584746000},"page":"175-186","source":"Crossref","is-referenced-by-count":41,"title":["Incorporating In Vitro Information on Drug Metabolism Into Clinical Trial Simulations to Assess the Effect of CYP2D6 Polymorphism on Pharmacokinetics and Pharmacodynamics: Dextromethorphan as a Model Application"],"prefix":"10.1002","volume":"47","author":[{"given":"Gemma L.","family":"Dickinson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed","family":"Rezaee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Proctor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin S.","family":"Lennard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey T.","family":"Tucker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Rostami\u2010Hodjegan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,7]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270005283463"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1994.93"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(77)91430-1"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(77)90527-X"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.2165\/00124363-200104000-00008"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2003.01853.x"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1975184377"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/00498250600683197"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1998.tb06914.x"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/00498250050119817"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/108705710100600404"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3550373"},{"key":"e_1_2_6_14_2","first-page":"1362","article-title":"Characterization of dextromethorphan O\u2010 and N\u2010demethylation catalyzed by highly purified recombinant human CYP2D6","volume":"29","author":"Yu A","year":"2001","journal-title":"Drug Metab Dispos."},{"key":"e_1_2_6_15_2","first-page":"1514","article-title":"Comparative contribution to dextromethorphan metabolism by cytochrome P450 isoforms in vitro: can dextromethorphan be used as a dual probe for both CTP2D6 and CYP3A activities","volume":"29","author":"Yu A","year":"2001","journal-title":"Drug Metab Dispos."},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1080\/00498250310001646353"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-199508000-00005"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.33215"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2004.07.001"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1006\/pupt.2001.0301"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(96)90056-9"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1999.00029.x"},{"issue":"1","key":"e_1_2_6_23_2","first-page":"74","article-title":"The propagation of genetic polymorphism in CYP2C9 into warfarin pharmacokinetics: an integrated model","volume":"37","author":"Dickinson GL","year":"2005","journal-title":"Drug Metab Rev."},{"issue":"1","key":"e_1_2_6_24_2","first-page":"148","article-title":"The propagation of genetic polymorphism in CYP2C9 into tolbutamide pharmacokinetics: assessment using an integrated model","volume":"38","author":"Dickinson G","year":"2006","journal-title":"Drug Metab Rev."},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.10128"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2004.10.014"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1177%2F0091270006294279","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1177\/0091270006294279","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:36:36Z","timestamp":1697157396000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1177\/0091270006294279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,2]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2007,2]]}},"alternative-id":["10.1177\/0091270006294279"],"URL":"https:\/\/doi.org\/10.1177\/0091270006294279","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,2]]}}}