Ethnic differences in the population pharmacokinetics and pharmacodynamics of warfarin.

Journal of Pharmacokinetics and Pharmacodynamics
Eunice YuenLeon Aarons

Abstract

Ethnic differences in warfarin maintenance doses have been documented amongst the three major Asian ethnic groups (Chinese, Malay and Indian) in Singapore. Studies have shown that cytochrome P450 2C9 (CYP2C9) polymorphisms alone did not entirely account for these differences. Recent reports suggest that VKORC1 (subunit of vitamin K epoxide reductase) haplotypes are more predictive of warfarin response. Population pharmacokinetic/pharmacodynamic (PK/PD) modelling techniques were employed to characterise the PK and PD of warfarin in a healthy volunteer study of 16 Chinese and Indian subjects following a single 25 mg dose of warfarin. To further investigate the underlying differences in warfarin response, a semi-mechanistic modelling approach (using an indirect response model for PCA activity) incorporating the vitamin K cycle was attempted using population methods with Bayesian inference. All eight Indian subjects had H7H7 VKORC1 haplotypes and three had either *2/wt or *3/wt CYP2C9 genotypes. Six Chinese subjects had H1H1 VKORC1 haplotypes and one had H1H7. All Chinese subjects were homozygous wt/wt for CYP2C9. Simulations to steady state were performed to examine warfarin response in subjects with different CYP2C9 and VKORC1 po...Continue Reading

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Citations

Mar 2, 2011·The Pharmacogenomics Journal·A PavaniV K Kutala
Jan 25, 2012·Journal of Pharmacokinetics and Pharmacodynamics·Kerenaftali KleinLeon Aarons
Nov 26, 2011·Thrombosis and Haemostasis·Todd S PerlsteinMark A Creager
Jan 6, 2011·British Journal of Clinical Pharmacology·Stephen B DuffullHelen R Winter
Jul 10, 2013·CPT: Pharmacometrics & Systems Pharmacology·L HarnischO Della Pasqua
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Aug 25, 2016·Therapeutic Advances in Cardiovascular Disease·Rohan Shah, Manesh R Patel
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Apr 26, 2014·Stroke; a Journal of Cerebral Circulation·Ka Sing Lawrence WongUNKNOWN Executive Steering Committee and the ROCKET AF Study Investigators
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Apr 15, 2017·Clinical Pharmacokinetics·Qing Xi OoiStephen B Duffull
Nov 5, 2019·Singapore Medical Journal·Rungroj KrittayaphongUNKNOWN Cool-AF Investigators

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