Evaluation of individual phenytoin dosage regimen based on genotyping of the CYP2C subfamily

We estimated the population pharmacokinetic parameters of phenytoin in Japanese patients with epilepsy, and examined the effect of cytochrome P450(CYP)2C9/19 polymorphisms on the pharmacokinetics of phenytoin. In this study, we evaluated the phenytoin dosage regimen based on the simple polymerase chain reaction-based genetic test of CYP2C isozymes. The population pharmacokinetic parameters without the information of CYP2C genotypes failed to predict the serum phenytoin concentration in patients with the mutation in CYP2C9 (Ile³⁵⁹→Leu). In contrast, the genotyping of CYP 2C9/19 in individual patients was useful in determining which patients are at risk for drug intoxication. In addition, the precision of the predicted serum phenytoin concentrations was improved by the Bayesian analysis based on the population pharmacokinetic parameters involving the polymorphism of CYP2C subfamily. The genetic test for the CYP2C isozymes will be useful to determine the dosage regimen of phenytoin.