EFFECT OF CYP2C POLYMORPHISMS ON THE PHARMACOKINETICS OF PHENYTOIN INJAPANESE PATIENTS WITH EPILEPSY

We examined the effect of CYP2C9/19 polymorphisms on the pharmacokinet ics of phenytoin in 17 Japanese patients with epilepsy. The maximal el imination rate (V-max) of phenytoin was slightly decreased (up to 14%) in patients with CYP2C19 mutations for the defective allele. The V-ma x values in patients with a CYP2C9 mutation for the heterozygous Ile/L eu(359) allele were 40% lower than those in patients with wild-type CY P2C9 for the homozygous Ile(359) allele. These findings suggested that the genetic polymorphism of CYP2C isoenzymes plays an important role in the pharmacokinetic variability of phenytoin, and that the mutation in CYP2C9 proteins is a determinant of impaired metabolism of the dru g.