PM frequencies of major CYPs in Asians and Caucasians.
Many administered drugs are first activated by phase I drug-metabolizing enzymes, such as cytochrome P450 (CYP), and then conjugated with ligands such as UDPGA, PAPS, and glutathione by phase II drug-metabolizing enzymes, and finally excreted by transporters. There are some defective activity mutants due to CYP polymorphisms. In these cases, drugs are not metabolized [poor metabolizer (PM)], the high drug levels in blood are maintained, and toxic effects appear in the patients. To clarify the ratio of PMs, in the general population, it is necessary to estimate the drug level to not only prevent toxic reactions, but also to provide more efficient drug therapies, according to their polymorphic information about CYPs. In Caucasians and Asians, PM and allele frequency levels of CYPs (CYP2A6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) are summarized from previous findings. In Caucasians, high PM ratios (7%) of CYP2D6 deriving from the high frequency of CYP2D6*4 and CYP2D6*5, and 2% CYP2C19 from CYP2C19*2, were found. Meanwhile, in Asians, high PM ratios (19%) of CYP2C19 from high frequencies of CYP2C19*2 and CYP2C19*3, and 2% to 4% CYP2A6 from CYP2A6*4, were found. In both populations, the PM frequencies of the CYP3A4 of major drug-metabolizing CYP and CYP2C9 were low.
Mizutani
Takaharu
T
Department of Drug Metabolism and Disposition, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan. mizutani@phar.nagoya-cu.ac.jp
D044466:Asian People / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics*
D003577:Cytochrome P-450 Enzyme System