{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:23:43Z","timestamp":1782231823706,"version":"3.54.5"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:p>Cytochrome P450 2C9 (CYP2C9) is responsible for the oxidative metabolism of about 15% of commonly used drugs, some of which are characterized by a narrow therapeutic window. <jats:italic>CYP2C9<\/jats:italic> is highly polymorphic, and over 60 alleles have been described. <jats:italic>CYP2C9*2<\/jats:italic> and <jats:italic>CYP2C9*3<\/jats:italic> are the most common polymorphisms among White patients and both are associated with decreased activity. The evidence concerning the functional importance of less frequent variant alleles is scarce. The objective of the current study was to characterize the <jats:italic>in vivo<\/jats:italic> activity of CYP2C9 among carriers of <jats:italic>CYP2C9*11<\/jats:italic>, one of the \"African\" alleles and the fourth most common <jats:italic>CYP2C9<\/jats:italic> variant allele among White patients by using two prototype substrates, phenytoin and (<jats:italic>S<\/jats:italic>)\u2010warfarin. Single 300\u2010mg phenytoin and 20\u2010mg warfarin doses were given to 150 healthy Ethiopian Jewish participants who were nonsmokers, at least one week apart. (<jats:italic>S<\/jats:italic>)\u2010warfarin oral clearance and phenytoin metabolic ratio (PMR) derived from the ratio of 5\u2010(4\u2010hydroxyphenyl)\u20105\u2010phenylhydantoin in 24\u2010hour urine collection to plasma phenytoin 12\u00a0hours (PMR 24\/12) or 24\u00a0hours (PMR 24\/24) post dosing, were used as markers of CYP2C9 activity. PMR 24\/12 and PMR 24\/24 were reduced by 50% and 62.2%, respectively, among carriers of <jats:italic>CYP2C9*1\/*11<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a013) as compared with carriers of <jats:italic>CYP2C9*1\/*1<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a0127) (false discovery rate (FDR) <jats:italic>q<\/jats:italic>\u00a0&lt;\u00a00.001). The respective decrease in (<jats:italic>S<\/jats:italic>)\u2010warfarin oral clearance was 52.6% (FDR <jats:italic>q<\/jats:italic>\u00a0&lt;\u00a00.001). In conclusion, the enzyme encoded by <jats:italic>CYP2C9*11<\/jats:italic> is characterized by a more than 50% decrease in the enzymatic activity, resembling the extent of decrease associated with <jats:italic>CYP2C9*3<\/jats:italic> (\"no\u2010function allele\"). Among patients of African ancestry, <jats:italic>CYP2C9*11<\/jats:italic> genetic analysis should be considered prior to prescribing of narrow therapeutic window drugs such as phenytoin, warfarin, nonsteroidal anti\u2010inflammatory drugs, or siponimod.<\/jats:p>","DOI":"10.1002\/cpt.2613","type":"journal-article","created":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T07:19:12Z","timestamp":1650007152000},"page":"156-163","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Impact of <i>CYP2C9*11<\/i> Allelic Variant on the Pharmacokinetics of Phenytoin and (<i>S<\/i>)\u2010Warfarin"],"prefix":"10.1111","volume":"112","author":[{"given":"Maor","family":"Wanounou","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Unit Division of Medicine Hadassah\u2010Hebrew University Medical Center Jerusalem Israel"},{"name":"Faculty of Medicine Institute of Drug Research School of Pharmacy Hebrew University Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanan","family":"Shaul","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit Division of Medicine Hadassah\u2010Hebrew University Medical Center Jerusalem Israel"},{"name":"Faculty of Medicine Institute of Drug Research School of Pharmacy Hebrew University Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahi","family":"Abu Ghosh","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit Division of Medicine Hadassah\u2010Hebrew University Medical Center Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoshana","family":"Alamia","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit Division of Medicine Hadassah\u2010Hebrew University Medical Center Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoseph","family":"Caraco","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit Division of Medicine Hadassah\u2010Hebrew University Medical Center Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.12.007"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm8010001"},{"key":"e_1_2_10_4_1","unstructured":"Pharmacogenomics Knowledgebase (PharmGKB).Gene\u2010specific information tables for CYP2C9<https:\/\/www.pharmgkb.org\/page\/cyp2c9RefMaterials>. 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