Hartley R, Forsythe W I, McLain B, Ng P C, Lucock M D
Paediatric Research Unit, University Department of Paediatrics and Child Health, Leeds, England.
Clin Pharmacokinet. 1991 Mar;20(3):237-46. doi: 10.2165/00003088-199120030-00005.
Total plasma carbamazepine, carbamazepine-10,11-epoxide (CBZ-EP) and 10,11-dihydro-10,11-trans-dihydroxy-carbamazepine (CBZ-DIOL) concentrations were measured during a 24h period in 21 patients receiving carbamazepine monotherapy, in equally divided doses, every 12h. Interdose and diurnal variations in plasma concentrations of parent drug and metabolites were assessed. Carbamazepine and both metabolites showed significant differences in mean 4h post-dose plasma concentrations between day and night dosing (p less than 0.001). Significant linear correlations were obtained between carbamazepine dose and plasma concentrations of carbamazepine, CBZ-EP and CBZ-DIOL when sampling times were standardised (p less than 0.01). Comparisons of plasma concentrations of the parent compound with those of its 2 main metabolites revealed significant linear correlations in all cases (p less than 0.01). The effects of daily fluctuations in plasma concentrations of all 3 compounds on their relative concentrations (CBZ-EP:carbamazepine, CBZ-DIOL:carbamazepine and CBZ-DIOL:CBZ-EP) during the 24h period were also determined: the plasma concentration ratios CBZ-EP:carbamazepine and CBZ-DIOL:carbamazepine were significantly related to the dose of carbamazepine at fixed sampling times (p less than 0.05, with 1 exception). The large interdose and diurnal variation in plasma carbamazepine concentrations observed in this study (approximately 40% decrease from peak to trough) has important implications both clinically and in relation to therapeutic drug monitoring.
在21例接受卡马西平单一疗法的患者中，每12小时给予等量的卡马西平，在24小时内测定了血浆中卡马西平、卡马西平-10,11-环氧化物（CBZ-EP）和10,11-二氢-10,11-反式-二羟基卡马西平（CBZ-DIOL）的总浓度。评估了母体药物及其代谢物血浆浓度的给药间期和昼夜变化。卡马西平和两种代谢物在白天和夜间给药后4小时的平均血浆浓度存在显著差异（p<0.001）。当采样时间标准化时，卡马西平剂量与卡马西平、CBZ-EP和CBZ-DIOL的血浆浓度之间存在显著的线性相关性（p<0.01）。母体化合物与其两种主要代谢物的血浆浓度比较在所有情况下均显示出显著的线性相关性（p<0.01）。还确定了这三种化合物血浆浓度的每日波动对其在24小时内相对浓度（CBZ-EP:卡马西平、CBZ-DIOL:卡马西平、CBZ-DIOL:CBZ-EP）的影响：在固定采样时间，血浆浓度比CBZ-EP:卡马西平和CBZ-DIOL:卡马西平与卡马西平剂量显著相关（p<0.05，有1例例外）。本研究中观察到的血浆卡马西平浓度的较大给药间期和昼夜变化（从峰值到谷值约降低40%）在临床和治疗药物监测方面都具有重要意义。
