The relationship between phenytoin pharmacokinetics and the CYP2C19 genotype in Japanese epileptic patients.
The relationship between the phenytoin pharmacokinetics, expressed by the mean of the Michaelis-Menten equation and the CYP2C19 genotype was investigated in 16 Japanese epileptic patients treated with phenytoin. Between genetically (S)-mephenytoin poor and extensive metabolizers, there were no differences in the Michaelis-Menten parameters. But divided into genotype groups, Vmax values were 3.9 +/- 0.4, 5.3 +/- 0.7, and 5.7 +/- 1.4 mg/kg/day for the patients with the m2 allele, with the m1 allele, and with neither the m1 or m2 allele, respectively. In the patients with the m2 allele of CYP2C19, the Vmax value was significantly lower than in those without the m2 allele. It is possible that the m2 allele of CYP2C19 may be one of the factors of slow phenytoin metabolism, and its frequency may underlie the ethnic difference in phenytoin metabolism between Japanese and white individuals.
Watanabe
M
M
Department of Neuropsychiatry, Kagawa Medical School, Japan.
Iwahashi
K
K
Kugoh
T
T
Suwaki
H
H
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000927:Anticonvulsants / Q000378:metabolism / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004827:Epilepsy / Q000201:enzymology* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D010672:Phenytoin / Q000378:metabolism / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D010672:Phenytoin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19