NONMEM法考察中国癫痫患者丙戊酸和卡马西平的药动学相互作用  

Investigation of valproic acid-carbamazepine interaction by mixed effect modeling in Chinese epilepsy patients

作　　者：焦正[1] 钟明康[1] 施孝金[1] 胡敏[1] 李中东[1] 王大猷[1] 张莉莉[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：《中国药学杂志》2004年第2期130-132,共3页Chinese Pharmaceutical Journal

基　　金：上海市卫生局百人计划项目资助(项目编号98BR009)

摘　　要：目的 考察中国癫痫患者中丙戊酸(VPA)和卡马西平(CBZ)的药物相互作用。方法 采用非线性混合效应模型,通过估算722例服用VPA和(或)CBZ的中国癫痫患者的清除率来定量考察两药的药动学相互作用。结果 VPA的清除率为CL=0.007 26×TBW0。890×(1+18.1DOSE)×1.36CBZ×1.22CHILD,CBZ的清除率为:CL=1.21×DOSE0.409×TBW0.292×1.16VPA×0.845ELDER,其中CL为清除率(L·h-1);TBW为体重(kg);DOSE为日剂量(g·kg-1·d-1);当服用CBZ时,CBZ=1,反之CBZ=0;当服用VPA且VPA日剂量大于19 mg·kg-1时,VPA=1,反之VPA=0;当小于6岁的儿童时CHILD=1,反之CHILD=0;当大于65岁的老人,ELDER=1,反之ELDER=0。结论 卡马西平和丙戊酸合用时,丙戊酸的清除率增加36％,当丙戊酸的日剂量大于19 mg·kg-1 时,卡马西平的清除率增加16％。OBJECTIVE: To investigate the valproic acid-carbamazepine interaction in Chinese epilepsy patients. METHODS: Nonlinear mixed effects modeling was used to estimate the effects of valproic acid-carbamazepine interaction on their clearance from 722 patients who received valproic acid and/or carbamazepine during their clinical routine care. RESULTS: The final model describing VPA clearance was: CL = 0.0072 6 × TBW0.890 × (1 + 18.1 DOSE) × 1.36CBZ × 1.22CHILD. The final model describing CBZ clearance was: CL = 1. 21 × DOSE0.409 × TBW0.292 × 1.16VPA × 0.845ELDER. Where CL was clearance (L&middoth-1), TBW was total body weight (kg), DOSE was daily dosage (g&middotd-1. kg-1). CBZ = 1 for concomitant administration of CBZ and CBZ = 0 for otherwise; VPA = 1, when VPA dose was higher than 19 mg&middotkg-1. CHILD for children less than 6 year and ELDER for people greater than 65 year. CONCLUSION: Concomitant adminstration of valproic acid and carbamazepine resulted in 36% increase in valproic acid clearance and 16% increase in carbamazepine clearance when valproic acid daily dose was greater than 19 mg&middotkg-1.

关 键 词：NONMEM法 中国 癫痫 丙戊酸 VPA 卡马西平 CBZ 药动学 血药浓度 

分 类 号：R742.1[医药卫生—神经病学与精神病学] R969.1[医药卫生—临床医学]