Abstract
Using population pharmacokinetic analysis (PPK), we attempted to identify predictors of S-warfarin clearance (CL(S)) and to clarify population differences in S-warfarin pharmacokinetics among a cohort of 378 African American, Asian and white patients. Significant predictors of CL(S) included clinical (age, body weight and sex) and genotypic (CYP2C9∗2,∗3 and ∗8) factors, as well as African American ethnicity, the median CL(S) being 30% lower in the latter than in Asians and whites (170 versus 243 and 250 ml h-1, P<0.01). The plasma S-warfarin (Cp(S)) time courses following the genotype-based dosing algorithms simulated using the PPK estimates showed African Americans with CYP2C9∗1/∗1 and any of the VKORC1 genotypes would have an average Cp(S) at steady state 1.5-1.8 times higher than in Asians and whites. These results indicate warfarin dosing algorithms should be evaluated in each respective ethnic population. Further study of a large African American cohort will be necessary to confirm the present findings.
Original language | English (US) |
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Pages (from-to) | 494-500 |
Number of pages | 7 |
Journal | Pharmacogenomics Journal |
Volume | 17 |
Issue number | 6 |
DOIs | |
State | Published - Dec 1 2017 |
ASJC Scopus subject areas
- Molecular Medicine
- Genetics
- Pharmacology