非线性混合效应模型考察丙戊酸、苯妥英和苯巴比妥对卡马西平及其环氧化代谢产物相对清除率的影响  

Investigation of influence of valproic acid, phenytoin, phenobarbital to relative clearance of carbamazepine and its epoxide metabolite

作　　者：焦正[1] 钟明康[1] 施孝金[1] 张静华[1] 王宏图[1] 

机构地区：[1]复旦大学华山医院临床药学研究室,上海200040

出　　处：《中国临床药理学杂志》2003年第5期359-363,共5页The Chinese Journal of Clinical Pharmacology

基　　金：上海市卫生系统百人计划资助项目(No.98BR009)

摘　　要：目的 考察丙戊酸(VPA)、苯妥英(PHT)和苯巴比妥(PB)对卡马西平(CBZ)及其环氧化代谢产物(CBZE)相对清除率(CL)的影响。方法 采集上海、北京、南京三地五所医院服用CBZ的408例癫痫患者的稳态血样(n=459)。数据分析时,用一级吸收和消除的药代动力学模型和非线性混合效应模型法。结果 合用VPA且其日剂量大于18mg·kg^(-1)·d^(-1),PHT或 PB会增加CBZ的CL;合用VPA会降低CBZE的CL。结论 可为中国癫痫患者卡马西平的临床个体化给药方案的制定提供依据。Objective To investigate the influence of valproic acid (VPA), phenytoin (PHT), phenobarbital(PB) to the clearance (CL) of carbamazepine(CBZ) and its epoxide metabolite (10,11-epoxide-carbamazepine, CBZE). Methods Steady state serum concentration data (n=459) were collected prospectively from 408 patients of 5 hospitals in Shanghai, Beijing and Nanjing during their routine clinical care. Nonlinear mixed effect model was used to estimate the relative clearance of CBZ and CBZE with a one-compartment model of first-order absorption and elimination. Results Comedication of VPA and its dose greater than 18 mg ·kg^(-1) ·d^(-1), PHT or PB can increase the CL of CBZ. In terms of CBZE, VPA can decrease its CL. Conclusion Population pharmacokinetic models for CBZ and CBZE are proposed to estimate the individual CL for Chinese patients receiving CBZ in order to establish an individualized dosage regimens.

关 键 词：丙戊酸 苯妥英 苯巴比妥 卡马西平 环氧化代谢产物 清除率 CL CBZE CBZ VPA PHT PB 

分 类 号：R969[医药卫生—药理学]