Assael B M, Bossi L, Garattini S, Gerna M, Gomeni R, Morselli P L
Arch Int Pharmacodyn Ther. 1976 Mar;220(1):125-39.
Adult, male, female and pregnant rats were treated with single and repeated doses of carbamazepine (CBZ). The time course of the drug concentrations in plasma and tissues was followed. In all cases, data on plasma levels were subjected to pharmacokinetic analyses. Attempts were made to relate pharmacokinetic properties of carbamazepine to its effect on pentobarbital sleeping time and on protection against electroshock, after acute and repeated administration: --it was found that male rats eliminate carbamazepine faster than females: the total body clearance (TBC) was 16 ml/min/kg and 9.4 ml/min/kg, respectively. Two dose levels (25 and 50 mg/kg) had the same pharmacokinetic properties in young rats. Pregnant rats clear CBZ to a lesser extent than controls. --CBZ was found to accelerate its own elimination after repeated administration in both adult and young rats as revealed by the shortening of its half-life and an increase of 50% in clearance. Moreover, the protection against electroshock was significantly reduced after repeated administration, compared with a single-dose administration. Repeated administration of CBZ in rats shortens pentobarbital sleeping time and decreases the pentobarbital brain level significantly.
成年雄性、雌性及怀孕大鼠接受了单次和重复剂量的卡马西平（CBZ）治疗。监测了药物在血浆和组织中的浓度随时间的变化过程。在所有情况下，均对血浆水平数据进行了药代动力学分析。在急性和重复给药后，尝试将卡马西平的药代动力学特性与其对戊巴比妥睡眠时间和电击防护作用的影响联系起来：——发现雄性大鼠消除卡马西平的速度比雌性大鼠快：总体清除率（TBC）分别为16毫升/分钟/千克和9.4毫升/分钟/千克。两个剂量水平（25和50毫克/千克）在幼鼠中具有相同的药代动力学特性。怀孕大鼠清除卡马西平的程度低于对照组。——在成年和幼鼠中，重复给药后均发现卡马西平会加速自身的消除，表现为其半衰期缩短且清除率增加50%。此外，与单次给药相比，重复给药后对电击的防护作用显著降低。在大鼠中重复给药卡马西平会缩短戊巴比妥睡眠时间并显著降低戊巴比妥在脑中的水平。
