Factors influencing pharmacokinetics of warfarin in African-Americans: implications for pharmacogenetic dosing algorithms.
Pharmacogenomics
; 16(3): 217-25, 2015.
Article
em En
| MEDLINE
| ID: mdl-25712185
ABSTRACT
AIM:
This study attempted to identify predictors of S-warfarin clearance (CL[S]) and to make a pharmacokinetic evaluation of genotype-based dosing algorithms in African-Americans.METHODS:
Using plasma S-warfarin concentration (Cp[S]) at a steady state and eight SNPs previously shown to influence warfarin dose in African-Americans, CL(S) and its predictors were estimated by population pharmacokinetic analysis in 60 African-Americans. The time courses of Cp(S) following either the loading dose or maintenance dose were simulated using the population pharmacokinetic estimates.RESULTS:
CYP2C9*8 and body surface area or body weight were predictors of CL(S) (-30 and -5% per -0.1 m(2)/-10 kg reduction in CL[S], respectively) in African-Americans. Simulations of Cp(S) showed that Cp(S) at steady state was 1.4-times higher in patients with CYP2C9*8 than in those with CYP2C9*1/*1, irrespective of the algorithm for loading dose or maintenance dose.CONCLUSION:
African-Americans possess independent predictors of CL(S), possibly leading to a prediction error of any dosing algorithm that excludes African-specific variant(s). Original submitted 3 September 2014; Revision submitted 3 November 2014.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Varfarina
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Negro ou Afro-Americano
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Citocromo P-450 CYP2C9
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Anticoagulantes
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article