Population differences in S-warfarin pharmacokinetics among African Americans, Asians and whites: their influence on pharmacogenetic dosing algorithms.
Pharmacogenomics J
; 17(6): 494-500, 2017 12.
Article
em En
| MEDLINE
| ID: mdl-27503578
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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Base de dados:
MEDLINE
Assunto principal:
Varfarina
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Negro ou Afro-Americano
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Povo Asiático
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População Branca
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Vitamina K Epóxido Redutases
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Citocromo P-450 CYP2C9
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Anticoagulantes
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article