Macphee G J, Butler E, Brodie M J
Epilepsia. 1987 May-Jun;28(3):286-94. doi: 10.1111/j.1528-1157.1987.tb04220.x.
Total and free carbamazepine (CBZ), and CBZ 10,11 epoxide (CBZ-E) concentrations were measured over 24 h in 19 patients receiving CBZ 400 mg b.i.d. either as monotherapy (n = 13) or combined with another anticonvulsant (n = 6). Differences in CBZ and CBZ-E disposition between day and night dosing were minor. Mean plasma CBZ concentrations were higher and CBZ-E/CBZ ratios were lower in the monotherapy patients. Variations in total and free plasma CBZ levels were comparable in the monotherapy and polypharmacy groups. Peak free and total CBZ concentrations coincided at approximately 4 h postdose. Free CBZ levels correlated significantly with total in each patient. The extent of variation in total plasma CBZ concentration during 24 h correlated significantly with antipyrine clearance in the monotherapy group. Circadian rhythms are unlikely to influence CBZ disposition to a clinically relevant extent. Measurement of peak and trough CBZ concentrations should improve the value of therapeutic drug monitoring. The diurnal variation in CBZ concentration appears related to the degree of autoinduction of metabolism and is substantial enough to warrant the development of a slow-release preparation of the drug.
对19例接受卡马西平（CBZ）400mg每日两次治疗的患者进行了24小时的总卡马西平和游离卡马西平（CBZ）以及卡马西平10,11环氧化物（CBZ-E）浓度测定，这些患者中13例接受单一疗法，6例联合使用另一种抗惊厥药。白天和夜间给药之间CBZ和CBZ-E处置的差异较小。单一疗法患者的平均血浆CBZ浓度较高，CBZ-E/CBZ比值较低。单一疗法组和联合用药组中总血浆CBZ水平和游离血浆CBZ水平的变化相当。游离CBZ和总CBZ浓度峰值在给药后约4小时同时出现。每位患者的游离CBZ水平与总CBZ水平显著相关。单一疗法组中24小时内总血浆CBZ浓度的变化程度与安替比林清除率显著相关。昼夜节律不太可能在临床上显著影响CBZ的处置。测量CBZ浓度的峰值和谷值应能提高治疗药物监测的价值。CBZ浓度的昼夜变化似乎与代谢的自身诱导程度有关，且幅度足以保证开发该药物的缓释制剂。
