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Twenty\u2010four healthy adults were grouped by genotype of<jats:italic>CYP2C19<\/jats:italic>and<jats:italic>CYP2D6<\/jats:italic>. After a single dose of 25 mg of amitriptyline, blood samples were collected and anticholinergic effects were measured. The extent of<jats:italic>N<\/jats:italic>\u2010demethylation of amitriptyline significantly decreased in subjects carrying two nonfunctional alleles of<jats:italic>CYP2C19<\/jats:italic>. The extent of hydroxylation of amitriptyline or nortriptyline was significantly reduced in subjects carrying two<jats:italic>CYP2D6<\/jats:italic>decreased functional alleles compared with those with no or one decreased functional allele. The overall metabolic pathway of amitriptyline was more likely to be dominated by<jats:italic>CYP2C19<\/jats:italic>than<jats:italic>CYP2D6<\/jats:italic>. The gene variations of<jats:italic>CYP2C19<\/jats:italic>and<jats:italic>CYP2D6<\/jats:italic>did not change the pharmacodynamic effect. The findings of this study will provide useful information on individualized drug treatment with amitriptyline considering both<jats:italic>CYP2D6<\/jats:italic>and<jats:italic>CYP2C19<\/jats:italic>gene variations.<\/jats:p>","DOI":"10.1111\/cts.12451","type":"journal-article","created":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T21:25:03Z","timestamp":1489526703000},"page":"93-101","source":"Crossref","is-referenced-by-count":26,"title":["A Study on<i>CYP2C19<\/i>and<i>CYP2D6<\/i>Polymorphic Effects on Pharmacokinetics and Pharmacodynamics of Amitriptyline in Healthy Koreans"],"prefix":"10.1111","volume":"10","author":[{"given":"S","family":"Ryu","sequence":"first","affiliation":[{"name":"Clinical Research Division National Institute of Food and Drug Safety Ministry of Food and Drug Safety Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Park","sequence":"additional","affiliation":[{"name":"Clinical Research Division National Institute of Food and Drug Safety Ministry of Food and Drug Safety Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JH","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical Research Division National Institute of Food and Drug Safety Ministry of Food and Drug Safety Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YR","family":"Kim","sequence":"additional","affiliation":[{"name":"Clinical Research Division National Institute of Food and Drug Safety Ministry of Food and Drug Safety Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HS","family":"Na","sequence":"additional","affiliation":[{"name":"Clinical Research Division National Institute of Food and Drug Safety Ministry of Food and Drug Safety Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HS","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics College of Medicine University of Ulsan Asan Medical Center Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HY","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics College of Medicine University of Ulsan Asan Medical Center Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"IY","family":"Hwang","sequence":"additional","affiliation":[{"name":"Clinical Research Division National Institute of Food and Drug Safety Ministry of Food and Drug Safety Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JG","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical Research Division National Institute of Food and Drug Safety Ministry of Food and Drug Safety Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZW","family":"Park","sequence":"additional","affiliation":[{"name":"Clinical Research Division National Institute of Food and Drug Safety Ministry of Food and Drug Safety Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WY","family":"Oh","sequence":"additional","affiliation":[{"name":"Clinical Research Division National Institute of Food and Drug Safety Ministry of Food and Drug Safety Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JM","family":"Kim","sequence":"additional","affiliation":[{"name":"Clinical Research Division National Institute of Food and Drug Safety Ministry of Food and Drug Safety Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SE","family":"Choi","sequence":"additional","affiliation":[{"name":"Clinical Research Division National Institute of Food and Drug Safety Ministry of Food and Drug Safety Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,14]]},"reference":[{"key":"e_1_2_9_1_1","first-page":"188","volume-title":"Hormone Analogues","author":"Sneader W.","year":"2006"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)01393-9"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1998.tb04399.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0090-9556(25)06572-9","article-title":"Demethylation and hydroxylation of amitriptyline, nortriptyline, and 10\u2010hydroxyamitriptyline in human liver microsomes","volume":"9","author":"Mellstrom B.","year":"1981","journal-title":"Drug Metab. 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