Arvidsson J, Nilsson H L, Sandstedt P, Steinwall G, Tonnby B, Flesch G
Department of Paediatrics, County Hospital Ryhov, Jönköping, Sweden.
J Child Neurol. 1995 Mar;10(2):114-7. doi: 10.1177/088307389501000209.
A suppository for rectal administration of carbamazepine has been developed for situations in which it is unsuitable to use the oral route of administration. In an open, controlled, within-patient study, the pharmacokinetics, clinical efficacy, and tolerability of carbamazepine slow-release tablets were compared with those of carbamazepine suppositories in children with epilepsy. The pharmacokinetic part of the study comprised 22 children, and an additional nine children were included in the clinical part of the study. Treatment with slow-release tablets was replaced for 7 days with carbamazepine suppositories in bioequivalent dosage. Clinical factors such as the rate of seizures and the local tolerability were studied, and an overall assessment of efficacy was made. In the pharmacokinetic part, 24-hour plasma concentration curves for carbamazepine and carbamazepine-10,11-epoxide were recorded. The plasma concentration profiles (minimum, maximum, and mean concentrations, fluctuation index, and area under the curve) for carbamazepine and the other metabolites did not show any significant differences between oral and rectal administration when the suppository dose was increased by 25% compared to the tablets. No increase in seizure frequency was detected, and the overall assessment was very good to good in 25 of the 29 epileptic children. Increased flatulence during treatment with suppositories was noted in two children, one had anal irritation, and one had nausea/vomiting. Treatment with carbamazepine slow-release tablets in children with epilepsy can be replaced by carbamazepine suppositories in 25% higher dosage, with good clinical effect and appropriate pharmacokinetic values, when it is unsuitable to use the common oral route of administration.
已开发出一种用于直肠给药的卡马西平栓剂，适用于不宜采用口服给药途径的情况。在一项开放性、对照性、患者自身对照研究中，对癫痫患儿使用卡马西平缓释片与卡马西平栓剂的药代动力学、临床疗效和耐受性进行了比较。该研究的药代动力学部分包括22名儿童，另有9名儿童纳入研究的临床部分。用生物等效剂量的卡马西平栓剂替代缓释片治疗7天。研究了癫痫发作率和局部耐受性等临床因素，并对疗效进行了总体评估。在药代动力学部分，记录了卡马西平和卡马西平-10,11-环氧化物的24小时血浆浓度曲线。当栓剂剂量比片剂增加25%时，卡马西平和其他代谢物的血浆浓度曲线（最低、最高和平均浓度、波动指数和曲线下面积）在口服和直肠给药之间未显示出任何显著差异。未检测到癫痫发作频率增加，29名癫痫患儿中有25名的总体评估为非常好至良好。两名儿童在用栓剂治疗期间出现肠胃气胀增加，一名儿童有肛门刺激，一名儿童有恶心/呕吐。当不宜采用普通口服给药途径时，癫痫患儿使用的卡马西平缓释片可用剂量高出25%的卡马西平栓剂替代，临床效果良好且药代动力学值合适。
