NONMEM法估算中国癫痫患者卡马西平的清除率

目的　考察中国癫痫患者卡马西平的群体药动学参数。方法　癫痫病例来自上海、北京两地 4所医院 ,采集服用卡马西平的 5 92例患者的稳态血药浓度 (n =70 3)。NONMEM程序估算分析时 ,采用一级吸收和消除的药动学模型并固定吸收速率、生物利用度和表观分布体积参数。结果　体重 (TBW )、剂量 (Dose)、合用丙戊酸钠 (VPA)且其日剂量大于 2 0mg·kg-1·d-1、苯妥英 (PHT)、苯巴比妥 (PB)和年龄大于 6 5岁的老年人 (ELDER)均为卡马西平清除率(CL)的影响因素。性别、合用氯硝西泮、妥吡酯不改变卡马西平的清除率。最终模型为 :CL(CL/F) (L/h) =1 32·Dose(g·kg-1·d-1) 0 42 1·TBW (kg) 0 .691·1 2 0 VPA·1 4 3PHT·1 14 PB·0 836 ELDER。讨论　根据中国癫痫患者的群体药动学模型 ,结合患者服用的剂量、体重和合并用药可估算其清除率 ,制定给药方案

The estimation of clearance of carbamazepine in chinese epileptic patients by NONMEM

AIM To investigate the pharmacokinetic profile of carbamazepine (CBZ) in Chinese epilepsy patients. METHODS Steady state serum concentration data( n =703) were collected prospectively from 592 patients of 4 hospitals in Shanghai and Beijing during their routine clinical care. The values of the absorption rate, bioavailability and volume of distribution were fixed according to the literature. Only population clearance (CL) was calculated by NONMEM program, with a one compartment model of first order absorption and elimination. RESULTS Total body weight (TBW), dose and comedication of valproic sodium (VPA) and its dose greater than 20 mg·kg -1 ·d -1 , phenytoin (PHT), phenobarbital (PB) and the elder greater than 65 (ELDER) were all important determinants of CL. Sex and comedication of clonazepam or topiramate did not influence the CL of CBZ. The final model for clearance was: CL(CL/F)(L/h)=1 32·Dose(g·kg -1 ·d -1 ) 0 421 ·TBW(kg) 0.691 ·1 20 VPA ·1 43 PHT ·1 14 PB ·0 836 ELDER . CONCLUSION A population pharmacokinetic model is proposed to estimate the individual CL for Chinese patients receiving CBZ in term of patient's dose, TBW and comedications, in order to establish a prior dosage regimen.