PHARMACOKINETICS A ND D ISPOSITION

Objective: The goal ofthis study was to de- termine the frequencies of allelic variants of CYP2B6 and CYP3A5 in the Japanese population. Methods: Genotyping of CYP2B6 (*2, *3, *4, *5, *6, and *7) and CYP3A5 (*2, *3, *4, *5 ,a nd*6) was carried out in 265 unrelated Japanese subjects by polymerase chain reaction (PCR), restriction fragment length poly- morphism and allele-specific, real-time PCR assays. Results: Allele frequencies for CYP2B6*2, *3, *4, *5, *6 ,a nd*7 in 256 Japanese subjects were 0.047, 0, 0.093, 0.011, 0.164, and 0, respectively. Ethnic variation in al- lele frequencies relative to that in Caucasian subjects was observed for CYP2B6*4 (0.093 vs 0.040), *5 (0.011 vs 0.109), *6 (0.164 vs 0.256), and *7 (0 vs 0.030). Allele frequencies for CYP3A5*2, *3, *4, *5, and *6 in 265 Japanese subjects were 0, 0.740, 0, 0.004, and 0, re- spectively. The frequency of the CYP3A5*1 allele is 2.8 times higher in Japanese than in Caucasians. Conclusions: Our results contribute to a better under- standing ofthe molecular basis ofethnic differences in drug response, which may help to improve individual- ization ofdrug therapy and offer a preliminary basis for more rational use ofdrugs that are substrates f or CYP2B6 and CYP3A5 in the Japanese population.