The effect of CYP2C19 genotypes on the pharmacokinetics of warfarin enantiomers

Journal of Clinical Pharmacy and Therapeutics
Tsukasa UnoTomonori Tateishi

Abstract

The aim of this study was to elucidate the pharmacokinetics and pharmacodynamics of warfarin enantiomers in relation to cytochrome P450 2C19 (CYP2C19) genotypes. Fourteen subjects, of whom seven were homozygous extensive metabolizers (hmEMs) and seven were poor metabolizers (PMs) for CYP2C19, were enrolled. After a single oral 10 mg dose of racemic warfarin, the plasma concentrations of the warfarin enantiomers and prothrombin time expressed as international normalized ratio (PT-INR) were measured over the course of 120 h. The mean plasma concentrations and elimination half-life of (R)-warfarin of all the subjects were about 2-fold greater than those of (S)-warfarin. Additionally, the area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) and the elimination half-life of (R)-warfarin in PMs were significantly greater than those in hmEMs (P = 0.0005 and P = 0.0101 respectively). The S/R ratios of AUC of warfarin enantiomers were 0.51 in hmEMs and 0.37 in PMs (P = 0.0052). Whereas no difference was found in all pharmacokinetic parameters of (S)-warfarin in hmEMs compared with PMs. No significant difference in PT-INR, used as a measure of anticoagulant effect, was found between the hmEMs and PMs. Th...Continue Reading

References

Jun 1, 1994·British Journal of Clinical Pharmacology·E ChanM Rowland
Dec 1, 1996·Clinical Pharmacology and Therapeutics·T KubotaT Ishizaki
Jan 1, 1997·Pharmacology & Therapeutics·L S Kaminsky, Z Y Zhang
Jan 28, 1999·Biochemical and Biophysical Research Communications·U YasarF Sjöqvist
Dec 24, 2002·Clinical Pharmacology and Therapeutics·Maria Gabriella ScordoRoberto Padrini
Apr 2, 2005·British Journal of Clinical Pharmacology·Jari J LiljaPertti J Neuvonen
Jun 3, 2005·The New England Journal of Medicine·Mark J RiederAllan E Rettie
Aug 8, 2006·Clinical Pharmacology and Therapeutics·Kyoko ObayashiRyuya Horiuchi

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Citations

Dec 14, 2011·The Pharmacogenomics Journal·S-A BacanuM R Nelson
Aug 15, 2013·Genetic Testing and Molecular Biomarkers·Yundan LiangBingying Xu
Mar 12, 2015·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yumiko Akamine
Feb 24, 2010·Journal of Clinical Pharmacy and Therapeutics·N R Srinivas
Apr 28, 2010·Clinica Chimica Acta; International Journal of Clinical Chemistry·Toshiharu GotoYoshihisa Abe
Sep 17, 2009·Journal of Clinical Pharmacy and Therapeutics·Takenori Niioka, Tsukasa Uno
Aug 24, 2011·Journal of Cardiac Surgery·Ashwini NadkarniIsidore Berenbaum
Jun 23, 2011·British Journal of Clinical Pharmacology·Steven LaneMunir Pirmohamed
Aug 2, 2008·The Journal of Toxicological Sciences·Mayumi IshizukaShoichi Fujita
Nov 26, 2011·Expert Review of Clinical Pharmacology·Gwendolyn A McMillinRobert C Pendleton
Oct 16, 2016·Drug Metabolism and Personalized Therapy·Isabel LópezCristina Belén García
Aug 13, 2010·Clinical Pharmacology and Therapeutics·A FrymoyerL Z Benet

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