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论文类型：期刊论文

发表时间：2018-07-01

发表刊物：INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS

收录刊物：SCIE

卷号：56

期号：7

页面范围：337-346

ISSN号：0946-1965

关键字：phenytoin (PHT) dosage; cytochrome P450 (CYP) 2C9; CYP2C19; polymorphism

摘要：Objective: Therapeutic response to phenytoin (PHT), a first-line antiepileptic drug (AED), is highly variable, in part likely due to genetic factors. Genetic polymorphisms in cytochrome P450 (CYP) 2C9 and CYP2C19 are expected to affect the metabolism of PHT and consequently affect its maintenance doses. We aimed to clarify the effects of genetic polymorphisms in both enzymes on daily PHT maintenance dosage in Asian epileptic patients by metaanalysis. Materials and methods: A systematic literature search was conducted in PubMed and EMBASE for relevant studies published prior to April 14, 2017. RevMan 5.2.3 software was used to analyze the relationship between CYP2C9/2C19 polymorphisms and PHT maintenance doses. Results: A total of 6 studies with 993 patients fulfilling the inclusion criteria were included in our meta-analysis. The homozygous and heterozygous CYP2C19 mutation group (i.e., CYP2C19*2/*2, CYP2C19*3/*3, or CYP2C19*2/*3 group) required significant decrease of PHT maintenance dose. The starting maintenance dose suggested in this group is 4.38 mg/kg/day. Patients with heterozygous CYP2C9 or both heterozygous CYP2C9 and CYP2C19 showed a trend but not a statistically-significant decrease of PHT dose, but dosage adjustment was recommended. Conclusion: The meta-analysis indicates that CYP2C9 and CYP2C19 polymorphisms are associated with lower PHT maintenance dosage in Asian epileptic patients. Ethnic differences can influence PHT maintenance dose.