Drug Metabolism and Pharmacokinetics
Online ISSN : 1880-0920
Print ISSN : 1347-4367
ISSN-L : 1347-4367
Regular Article
Bioinformatics Research on Inter-racial Difference in Drug Metabolism I. Analysis on Frequencies of Mutant Alleles and Poor Metabolizers on CYP2D6 and CYP2C19
Takako SHIMIZUHirohide OCHIAIFredrik ÅSELLHiroshi SHIMIZURyuta SAITOHYoshimasa HAMAJun KATADAMunehiro HASHIMOTOHitoshi MATSUIKatsuhiko TAKITsuguchika KAMINUMAMichiko YAMAMOTOYoshitaka AIDAAkira OHASHINaoki OZAWA
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2003 Volume 18 Issue 1 Pages 48-70

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Abstract
The enzyme activities of CYP2D6 and CYP2C19 show a genetic polymorphism, and the frequency of poor metabolizers (PMs) on these enzymes depends on races. In the present study, the frequencies of mutant alleles and PMs in each race were analyzed based on information from published studies, considering the genetic polymorphisms of CYP2D6 and CYP2C19 as the causal factors of racial and inter-individual differences in pharmacokinetics. As a result, it was shown that there were racial differences in the frequencies of each mutant allele and PMs. The frequencies of PMs on CYP2D6 are 1.9% of Asians and 7.7% of Caucasians, and those of PMs on CYP2C19 are 15.8% of Asians and 2.2% of Caucasians. Based on the results, it was suggested that there would be racial differences in the frequencies of PM subjects whose blood concentrations might be higher for drugs metabolized by these enzymes. Additionally, it was suggested that enzyme activities would vary according to the number of functional alleles even in subjects judged to be extensive metabolizers (EMs). In the bridging study, genetic information regarding CYP2D6 and CYP2C19 of the subjects will help extrapolate foreign clinical data to a domestic population.
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© 2003 by The Japanese Society for the Study of Xenobiotics
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