Contributions of CYP2C9/CYP2C19 genotypes and drug interaction to the phenytoin treatment in the Korean epileptic patients in the clinical setting.
We examined the contribution of CYP2C9 and CYP2C19 genotypes and drug interactions to the phenytoin metabolism among 97 Korean epileptic patients to determine if pharmacogenetic testing could be utilized in routine clinical practice. The CYP2C9 polymorphism is a wellknown major genetic factor responsible for phenytoin metabolism. The CYP219 polymorphism, with a high incidence of variant alleles, has a minor influence on phenytoin treated Koran patients. Using a multiple regression model for evaluation of the CYP2C9 and CYP2C19 genotypes, together with other non-genetic variables, we explained 39.6% of the variance in serum phenytoin levels. Incorporation of genotyping for CYP2C9 and CYP2C19 into a clinical practice may be of some help in the determination of phenytoin dosage. However, because concurrent drug treatment is common in patients taking phenytoin and many environmental factors are likely to play a role in drug metabolism, these factors may overwhelm the relevance of CYP polymorphisms in the clinical setting. Further investigations with an approach to dose assessment that includes comprehensive interpretation of both pharmacogenetic and pharmacokinetic data along with understanding of the mechanism of drug interactions in dosage adjustment is warranted.
Lee
Soo-Youn
SY
Department of Laboratory Medicine and Genetics, Sungkyunkwan University School of Medicine and Samsung Medical Center, Seoul, Korea.
Lee
Seung-Tae
ST
Kim
Jong-Won
JW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D001499:Bayes Theorem; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D004827:Epilepsy / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007700:Kinetics; D007723:Korea; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D010672:Phenytoin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D012044:Regression Analysis
D000927:Anticonvulsants; D010672:Phenytoin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19