S-Space College of Medicine/School of Medicine (의과대학/대학원) Pharmacology (약리학전공) Journal Papers (저널논문_약리학전공)
Pharmacokinetics/genotype associations for major cytochrome P450 enzymes in native and first- and third-generation Japanese populations: comparison with Korean, Chinese, and Caucasian populations
- Myrand, S. P.; Sekiguchi, K.; Man, M. Z.; Lin, X.; Tzeng, R. Y.; Teng, C. H.; Hee, B.; Garrett, M.; Kikkawa, H.; Lin, C. Y.; Eddy, S. M.; Dostalik, J.; Mount, J.; Azuma, J.; Fujio, Y.; Jang, I. J.; Shin, S. G.; Bleavins, M. R.; Williams, J. A.; Paulauskis, J. D.; Wilner, K. D.
- Issue Date
- Clin Pharmacol Ther. 2008 Sep;84(3):347-61. Epub 2008 Mar 19.
- Alleles; Clinical Trials, Phase III as Topic; Cytochrome P-450 Enzyme System/blood/*genetics/metabolism; European Continental Ancestry Group/genetics; Far East; *Genetics, Population; *Genotype; Humans; Japan; Multicenter Studies as Topic; *Pharmacokinetics
- 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.
- 1532-6535 (Electronic)
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