Pharmacokinetics/Genotype Associations for Major Cytochrome P450 Enzymes in Native and First‐ and Third‐generation Japanese Populations: Comparison With Korean, Chinese, and Caucasian Populations

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...

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Published in:Clinical pharmacology and therapeutics 2008-09, Vol.84 (3), p.347-361
Main Authors: Myrand, SP, Sekiguchi, K, Man, MZ, Lin, X, Tzeng, R‐Y, Teng, C‐H, Hee, B, Garrett, M, Kikkawa, H, Lin, C‐Y, Eddy, SM, Dostalik, J, Mount, J, Azuma, J, Fujio, Y, Jang, I‐J, Shin, S‐G, Bleavins, MR, Williams, JA, Paulauskis, JD, Wilner, KD
Format: Article
Language:English
Subjects:
Alleles
Biological and medical sciences
Clinical Trials, Phase III as Topic
Cytochrome P-450 Enzyme System - blood
Cytochrome P-450 Enzyme System - genetics
Cytochrome P-450 Enzyme System - metabolism
European Continental Ancestry Group - genetics
Far East
Genetics, Population
Genotype
Humans
Japan
Medical sciences
Multicenter Studies as Topic
Pharmacokinetics
Pharmacology. Drug treatments
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Summary: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. Clinical Pharmacology & Therapeutics (2008); 84, 3, 347–361 doi:10.1038/sj.clpt.6100482
ISSN:0009-9236
1532-6535
DOI:10.1038/sj.clpt.6100482