Ramsay R E, McManus D Q, Guterman A, Briggle T V, Vazquez D, Perchalski R, Yost R A, Wong P
Department of Neurology, University of Miami, Florida 33136.
Ther Drug Monit. 1990 May;12(3):235-41. doi: 10.1097/00007691-199005000-00004.
Free and total carbamazepine (CBZ) and carbamazepine-epoxide (CBZ-EP) plasma levels were obtained on 113 patients with epilepsy (18-61 years old) controlled on either monotherapy or coadministration with either phenobarbital (PB), phenytoin (PHT), valproic acid (VPA), or all three. A subset of patients were administered tetradeuterium labeled CBZ to evaluate the effects of autoinduction and coadministration of VPA on the kinetics of CBZ and its metabolite CBZ-EP. Polytherapy had variable effect on free and total CBZ plasma levels compared to monotherapy. Coadministered PHT (co-PHT), or all three anticonvulsants together (PHT, PB, and VPA: co-AEDs) decreased free and total CBZ plasma levels. No change was noted for coadministered VPA (co-VPA). Compared to monotherapy the free and total CBZ-EP levels increased with co-VPA, less with coadministered PB (co-PB), and no change with co-PHT or co-AEDs. Protein binding of CBZ and CBZ-EP was not affected by any antiepileptic drugs studied. The free and total CBZ-EP/CBZ ratio was tripled with co-VPA or co-AED's, and doubled with co-PHT or co-PB. Isotope labeling did not demonstrate any differences in half-life (t1/2), plasma clearance (Cl), or volume of distribution (Vd). Compared to naive controls, monotherapy and co-VPA decreased CBZ t1/2 by 50%, and more than doubled the CBZ Cl without a significant change in the Vd. Autoinduction is one explanation for these changes with chronic CBZ therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
对113例癫痫患者（年龄18 - 61岁）进行了游离及总卡马西平（CBZ）和卡马西平环氧化物（CBZ - EP）血浆水平检测，这些患者接受单药治疗或与苯巴比妥（PB）、苯妥英（PHT）、丙戊酸（VPA）联合用药，或同时使用这三种药物。对部分患者给予氘代标记的CBZ，以评估自身诱导作用及VPA联合用药对CBZ及其代谢产物CBZ - EP动力学的影响。与单药治疗相比，联合治疗对游离及总CBZ血浆水平的影响各异。联合使用PHT（co - PHT）或三种抗惊厥药物一起（PHT、PB和VPA：co - AEDs）会降低游离及总CBZ血浆水平。联合使用VPA（co - VPA）时未观察到变化。与单药治疗相比，联合使用VPA时游离及总CBZ - EP水平升高，联合使用PB（co - PB）时升高较少，联合使用PHT或co - AEDs时无变化。所研究的任何抗癫痫药物均未影响CBZ和CBZ - EP的蛋白结合。联合使用VPA或co - AEDs时，游离及总CBZ - EP/CBZ比值增加两倍，联合使用PHT或co - PB时增加一倍。同位素标记未显示半衰期（t1/2）、血浆清除率（Cl）或分布容积（Vd）有任何差异。与未用药对照组相比，单药治疗和联合使用VPA使CBZ的t1/2降低50%，CBZ的Cl增加一倍多，而Vd无显著变化。自身诱导是慢性CBZ治疗导致这些变化的一种解释。（摘要截选至250字）
