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CYP2C19 genotype determines enzyme activity and inducibility of S-mephenytoin hydroxylase
1Pharmacogenetics Research Institute, Hunan Medical University, 410078, Hunan, Changsha, PR China. hhzhou@public.cs.hn.cn
Background:
The association between decreased drug clearance and decreased activity of cytochrome P4502C19 (CYP2C19), the inherited nature of the deficiency, and its frequency and clinical importance were evaluated extensively in the past over one decade. There is an interethnic difference in the frequency of poor metabolizers and mutant alleles of CYP2C19 among Chinese nationalities. Different frequency of mutations that code for CYP2C19 results in interethnic differences in distribution of the polymorphic trait for this enzyme. CYP2C19 genotype is a major determined factor for metabolisms of S-mephenytoin (S-MP), diazepam, and omeprazole (OP). The formations of their metabolites, 4'-hydroxymephenytoin (4'-OH-MP), demethyldiazepam, and 5-hydroxyomeprazole (5-OH-OP) are CYP2C19 genotype dependent. The inducibility of CYP2C19 activity is also related to CYP2C19 genotype.
Conclusions:
The availability of phenotyping and genotyping methods should help identify the adverse reaction and toxicity of drugs that metabolized by CYP2C19 and determine the doses of these drugs according to individual CYP2C19 genotype.