卡马西平及其主要代谢产物的自动诱导和稳态药代动力学
Autoinduction and steady-state pharmacokinetics of carbamazepine and its major metabolites.
作者信息
Kudriakova T B, Sirota L A, Rozova G I, Gorkov V A
机构信息
Mental Health Research Centre Russian AMS, Moscow.
出版信息
Br J Clin Pharmacol. 1992 Jun;33(6):611-5. doi: 10.1111/j.1365-2125.1992.tb04089.x.
Abstract
- The effect of carbamazepine (CBZ) dose change on mean plasma concentrations of CBZ, its two metabolites and apparent steady-state clearance was studied in 77 affectively ill patients receiving CBZ at doses of 100-1200 mg day-1. 2. Autoinduction of CBZ metabolism appeared to be complete within 1 week of starting CBZ therapy or dose change, and its degree was linearly related to CBZ daily dose. 3. Curvilinear plots were obtained for steady-state concentrations of CBZ and its -10,11-epoxide metabolite, and for the ratio of CBZ-10,11-epoxide to CBZ level, versus daily dose of CBZ. 4. On the contrary, steady-state concentration of CBZ-10,11-diol increased proportionately with the dose. This indicates that there is no dose dependency in absorption of CBZ, and that dose-dependent autoinduction of CBZ metabolism is the main cause of the curvilinear relationship between dose and steady-state concentration of CBZ and its intermediary metabolite, CBZ-10,11-epoxide.
摘要
- 在77例接受剂量为100 - 1200毫克/天卡马西平（CBZ）治疗的情感障碍患者中，研究了卡马西平剂量变化对其平均血浆浓度、两种代谢产物及表观稳态清除率的影响。2. 卡马西平代谢的自身诱导似乎在开始卡马西平治疗或剂量改变后的1周内完成，其程度与卡马西平每日剂量呈线性相关。3. 获得了卡马西平及其10,11 - 环氧化物代谢产物的稳态浓度以及卡马西平 - 10,11 - 环氧化物与卡马西平水平之比相对于卡马西平每日剂量的曲线。4. 相反，卡马西平 - 10,11 - 二醇的稳态浓度随剂量成比例增加。这表明卡马西平的吸收不存在剂量依赖性，且卡马西平代谢的剂量依赖性自身诱导是剂量与卡马西平及其中间代谢产物卡马西平 - 10,11 - 环氧化物稳态浓度之间曲线关系的主要原因。
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