Differences in Warfarin Pharmacodynamics and Predictors of Response Among Three Racial Populations

Clinical Pharmacokinetics
Minami OharaHarumi Takahashi

Abstract

Population differences in warfarin dosing requirement have been reported; however, unlike the pharmacokinetics (PK) of warfarin, the quantitative influences of pharmacodynamic (PD) factors on the anticoagulation response to warfarin in different ethnic populations are totally unknown. Using population PK/PD analysis, we attempted to identify predictors of S-warfarin clearance [CL(S)] and half maximal effective concentration (EC50) to quantify racial differences in both PK and PD parameters, and to assess the contribution of these parameters to the international normalized ratio (INR) and over-anticoagulation response (INR ≥ 4) in a cohort of 309 White, Asian and African American patients. Similar to our previous findings, the median CL(S) was 30% lower in African American patients than Asian and White patients (169 vs. 243 and 234 mL/h, p < 0.01). EC50 showed a greater racial difference than CL(S) [1.03, 1.70 and 2.76 μg/mL for Asian, White and African American patients, respectively, p < 0.01). Significant predictors of INR included demographic/clinical (age, body weight, creatinine clearance and sex) and genotypic (CYP2C9*3,*8 and VKORC1 -1639G>A) factors, as well as African American ethnicity. In all three racial groups, gen...Continue Reading

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Citations

Mar 14, 2020·Journal of Clinical Pharmacy and Therapeutics·Rashmi R Shah
Jan 12, 2020·Clinical Chemistry and Laboratory Medicine : CCLM·Camille RiffIsabelle Benz-de Bretagne
Oct 20, 2020·Frontiers in Pharmacology·Zahi Abu GhoshYoseph Caraco
Jan 27, 2021·International Journal of Molecular Sciences·Song GaoDong Liang

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