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

The Pharmacogenomics Journal volume 17, pages 494–500 (2017)Cite this article

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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.

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Acknowledgements

This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (KAKENHI C, 20590548), the Department of Health, Taiwan (DOH101-TD-PB-111-TM005), and an American Heart Association Midwest Affiliate Spring 2010 Grant-in Aid (10GRNT3750024).

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Author notes

  1. K Kubo and M Ohara: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan

    K Kubo, M Ohara, M Tachikawa, A Miyajima, N Kaneko & H Takahashi

  2. Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA

    L H Cavallari

  3. Genomic Medicine Institute, Geisinger Health System, Danville, PA, USA

    M T M Lee

  4. Division of Epidemiology and Genetics, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    M T M Lee & Y T Chen

  5. Department of Internal Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan

    M S Wen

  6. Department of Medical Sciences, Clinical Pharmacology, Uppsala University Hospital, Uppsala, Sweden

    M G Scordo

  7. Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA

    E A Nutescu

  8. Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, IL, USA

    M A Perera

  9. Department of Cardiothoracic and Vascular Sciences, University of Padova, Padova, Italy

    V Pengo

  10. Department of Medicine DIMED, University of Padova, Padova, Italy

    R Padrini

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  1. K Kubo
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Correspondence to H Takahashi.

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Kubo, K., Ohara, M., Tachikawa, M. et al. Population differences in S-warfarin pharmacokinetics among African Americans, Asians and whites: their influence on pharmacogenetic dosing algorithms. Pharmacogenomics J 17, 494–500 (2017). https://doi.org/10.1038/tpj.2016.57

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