Pharmacokinetics/genotype associations for major cytochrome P450 enzymes in native and first- and third-generation Japanese populations: comparison with Korean, Chinese, and Caucasian populations.
Clin Pharmacol Ther
; 84(3): 347-61, 2008 Sep.
Article
em En
| MEDLINE
| ID: mdl-18231117
ABSTRACT
Application of foreign clinical data across geographic regions can accelerate drug development. Drug disposition can be variable, and identification of factors influencing responsible pharmacokinetic/pharmacogenomic approaches could facilitate the universal application of foreign data and reduce the total amount of phase III clinical trials evaluating risks in different populations. Our objective was to establish and compare genotype (major cytochrome P450 (CYP) enzymes)/phenotype associations for Japanese (native and first- and third-generation Japanese living abroad), Caucasian, Chinese, and Korean populations using a standard drug panel. The mean metabolic ratios (MRs) for the four ethnic groups were similar except for a lower activity of CYP2D6 in Caucasians and CYP2C19 in Asians. Genotype, not ethnicity, impacted the MR for CYP2C9, CYP2C19, and CYP2D6; neither affected CYP1A2, CYP2E1, and CYP3A4/5 activities. We conclude that equivalent plasma drug concentrations and metabolic profiles can be expected for native Japanese, first- and third-generation Japanese, Koreans, and Chinese for compounds handled through these six CYP enzymes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Farmacocinética
/
Sistema Enzimático do Citocromo P-450
/
Genética Populacional
/
Genótipo
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos