TY - JOUR
T1 - Evaluation of phenytoin dosage regimen based on the genetic test of CYP2C subfamily
AU - Hashimoto, Y.
AU - Uwai, U.
AU - Odani, A.
AU - Hattori, H.
AU - Iniu, K.
PY - 1999
Y1 - 1999
N2 - We have estimated the population pharmacokinetic parameters of phenytoin in Japanese patients with epilepsy (Biol. Pharm. Bull., 19, 444, 1996), and examined the effect of cytochrome P450 (CYP) 2C9/19 polymorphisms on the pharmacokinetics of phenytoin (Clin. Pharmacol. Ther., 62, 287, 1997). 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 CYP2C9/19 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 in designing the dosage of phenytoin.
AB - We have estimated the population pharmacokinetic parameters of phenytoin in Japanese patients with epilepsy (Biol. Pharm. Bull., 19, 444, 1996), and examined the effect of cytochrome P450 (CYP) 2C9/19 polymorphisms on the pharmacokinetics of phenytoin (Clin. Pharmacol. Ther., 62, 287, 1997). 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 CYP2C9/19 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 in designing the dosage of phenytoin.
UR - http://www.scopus.com/inward/record.url?scp=33749097429&partnerID=8YFLogxK
U2 - 10.1016/S0009-9236(99)80199-4
DO - 10.1016/S0009-9236(99)80199-4
M3 - 学術論文
AN - SCOPUS:33749097429
SN - 0009-9236
VL - 65
SP - 167
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
IS - 2
ER -