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  • Kubo, K.Meiji Pharmaceut Univ, Dept Biopharmaceut, Noshio 2-522-1, Tokyo, Japan. (author)

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

  • Article/chapterEnglish2017

Publisher, publication year, extent ...

  • 2016-08-09
  • NATURE PUBLISHING GROUP,2017
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-343565
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-343565URI
  • https://doi.org/10.1038/tpj.2016.57DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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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  • Ohara, M.Meiji Pharmaceut Univ, Dept Biopharmaceut, Noshio 2-522-1, Tokyo, Japan. (author)
  • Tachikawa, M.Meiji Pharmaceut Univ, Dept Biopharmaceut, Noshio 2-522-1, Tokyo, Japan. (author)
  • Cavallari, L. H.Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA.;Univ Florida, Ctr Pharmacogen, Gainesville, FL USA. (author)
  • Lee, M. T. M.Geisinger Hlth Syst, Genom Med Inst, Danville, PA USA.;Acad Sinica, Inst Biomed Sci, Div Epidemiol & Genet, Taipei, Taiwan. (author)
  • Wen, M. S.Chang Gung Univ, Coll Med, Dept Internal Med, Taoyuan, Taiwan. (author)
  • Scordo, Gabriella MariaUppsala universitet,Klinisk farmakogenomik och osteoporos(Swepub:uu)gasco020 (author)
  • Nutescu, E. A.Univ Illinois, Dept Pharm Practice, Chicago, IL USA. (author)
  • Perera, M. A.Univ Chicago, Med Genet Sect, Dept Med, Chicago, IL USA. (author)
  • Miyajima, A.Meiji Pharmaceut Univ, Dept Biopharmaceut, Noshio 2-522-1, Tokyo, Japan. (author)
  • Kaneko, N.Meiji Pharmaceut Univ, Dept Biopharmaceut, Noshio 2-522-1, Tokyo, Japan. (author)
  • Pengo, V.Univ Padua, Dept Cardiothorac & Vasc Sci, Padua, Italy. (author)
  • Padrini, R.Univ Padua, Dept Med DIMED, Padua, Italy. (author)
  • Chen, Y. T.Acad Sinica, Inst Biomed Sci, Div Epidemiol & Genet, Taipei, Taiwan. (author)
  • Takahashi, H.Meiji Pharmaceut Univ, Dept Biopharmaceut, Noshio 2-522-1, Tokyo, Japan. (author)
  • Meiji Pharmaceut Univ, Dept Biopharmaceut, Noshio 2-522-1, Tokyo, Japan.Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA.;Univ Florida, Ctr Pharmacogen, Gainesville, FL USA. (creator_code:org_t)

Related titles

  • In:The Pharmacogenomics Journal: NATURE PUBLISHING GROUP17:6, s. 494-5001470-269X1473-1150

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