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Pharmacokinetics/Genotype Associations for Major Cytochrome P450 Enzymes in Native and First‐ and Third‐generation Japanese Populations: Comparison With Korean, Chinese, and Caucasian Populations
Author(s) -
Myrand SP,
Sekiguchi K,
Man MZ,
Lin X,
Tzeng RY,
Teng CH,
Hee B,
Garrett M,
Kikkawa H,
Lin CY,
Eddy SM,
Dostalik J,
Mount J,
Azuma J,
Fujio Y,
Jang IJ,
Shin SG,
Bleavins MR,
Williams JA,
Paulauskis JD,
Wilner KD
Publication year - 2008
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100482
Subject(s) - cyp2c19 , pharmacogenomics , cyp2d6 , pharmacokinetics , cyp1a2 , cyp2c9 , pharmacology , genotype , cyp3a4 , cytochrome p450 , drug , drug metabolism , clinical pharmacology , medicine , ethnic group , biology , genetics , gene , metabolism , sociology , anthropology
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