CYP3A5*3基因多态性对癫痫患者卡马西平及其主要代谢物浓度的影响  

Effects of CYP3A5*3 Genetic Polymorphisms on Serum Concentrations in People with Epilepsy

作　　者：张芹[1,2] 唐辉[1] 姬利红 张焕云 李乐[1] 

机构地区：[1]石河子大学药学院,新疆石河子832002 [2]鹤壁市人民医院,河南鹤壁458030

出　　处：《现代生物医学进展》2016年第27期5262-5265,共4页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81260627)

摘　　要：背景:卡马西平(carbamazepine,CMZP)主要由CYP3A酶家族代谢,其代谢酶主要包括CYP3A5。本研究探讨了CYP3A5基因多态性与卡马西平血清浓度(CMZP)之间的关系,对个体化药物治疗的开展具有十分积极的意义。目的:CYP3A5*3的基因型可以影响CYP3A药物的药代动力学。本研究旨在评估CYP3A基因多态性对癫痫患者血清卡马西平稳态浓度及其代谢物水平的影响。方法:研究共纳入278例患者,检测个体卡马西平的血清浓度及CYP3A5基因型,并探讨CYP3A5基因型对卡马西平稳态血药浓度的影响。结果:根据基因型分为成CYP3A5表达组(CYP3A5*1/*1和CYP3A5*1/*3)和非表达组(CYP3A5*3/*3)两组。278例患者中120例为CYP3A5表达组,158例患者为CYP3A5非表达组。CYP3A5非表达组的总卡马西平剂量和剂量标准化后的卡马西平血清浓度均高于CYP3A5表达组(P=0.608和P=0.000)。CYP3A5表达组中卡马西平环氧化物浓度更高(P=0.000),但这两组间的血清药物浓度无显著差异(P=0.090)。结论:CYP3A5*3基因多态性与卡马西平的血清浓度之间有密切的关系。CYP3A5基因影响了卡马西平血药浓度水平和代谢过程,其可能是导致卡马西平在癫痫患者中个体变异的一个重要因素。Background： Carbamazepine（CMZP） mainly metabolize by CYP3 A enzyme family, which includes enzyme CYP3A5.This study investigated the relationship between CYP3A5 gene polymorphism and serum concentration of carbamazepine. Objective：CYP3A5 ＊ 3 genotype CYP3 A can affect the pharmacokinetics of carbamazepine. This study aimed to assess the impact of CYP3 A gene polymorphism on the steady-state serum concentrations of carbamazepine and its metabolite levels in patients with epilepsy. Methods： A total of 278 cases of patients, serum concentrations of carbamazepine and CYP3A5 genotype of individuals were collected, and the impact of CYP3A5 genotype on steady-state plasma concentrations of carbamazepine were analysis. Results： According to the expression of CYP3A5 genotype,we divided all patients into two groups,CYP3A5 expression group（CYP3A5 ＊ 1 / ＊ 1 and CYP3A5 ＊ 1 / ＊ 3） and non-expression group（CYP3A5 ＊ 3 / ＊ 3） groups. 120 cases in CYP3A5 expression group, 158 cases of patients in CYP3A5 non-expressing group. Carbamazepine serum concentrations and it’s normalized dose in CYP3A5 expression group were higher than the CYP3A5 non-expression group（P=0.608 and P=0.000）. And the carbamazepine epoxide concentration in CYP3A5 expression group was much higher（P=0.000）, but no significance carbamazepine serum concentrations difference was detected between the two groups（P=0.090）. Conclusion： There is a close relationship between CYP3A5 ＊ 3 polymorphism and serum concentrations of carbamazepine.CYP3A5 gene can affects the plasma concentration of carbamazepine levels and metabolic processes, which may be an important factor leading to carbamazepine individual variation in epilepsy patients.

关 键 词：卡马西平 CYP3A5＊3 基因多态性 药物浓度监测 癫痫 清除率 个体差异 

分 类 号：R742.1[医药卫生—神经病学与精神病学]