Population differences in S-warfarin pharmacokinetics among African Americans, Asians and whites: Their influence on pharmacogenetic dosing algorithms

K. Kubo, M. Ohara, M. Tachikawa, L. H. Cavallari, M. T M Lee, M. S. Wen, M. G. Scordo, E. A. Nutescu, M. A. Perera, A. Miyajima, N. Kaneko, V. Pengo, R. Padrini, Y. T. Chen, H. Takahashi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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 languageEnglish (US)
Pages (from-to)494-500
Number of pages7
JournalPharmacogenomics Journal
Volume17
Issue number6
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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