Plasma Levels and Clinical Pharmacology of Antiepileptic Drugs in Children

在过去的10年里，通过将药代动力学数据应用于癫痫的药物治疗，癫痫的治疗取得了较好的效果。然而，儿童药物治疗的复杂性在于体重和身体成分随着生长发育的不断变化，采用前瞻性随机对照的方法，研究了苯妥英、卡马西平(CBZ)或丙戊酸钠(VPA)单药治疗不同类型癫痫发作时的血药浓度和癫痫控制情况。对新转诊的、以前未接受治疗的儿童的研究表明，这三种药物中的每一种都可以预防部分性和全身性强直-阵挛发作。当维持最佳血药浓度范围并监测血药浓度时，三种药物之间的临床疗效没有显著差异。氯硝西平(CZP)可能对部分性癫痫有效。然而，由于大范围的血浆浓度与完全免于癫痫发作有关，因此不可能确定CZP的治疗范围。任何接受多药治疗的患者都有发生药物-药物相互作用的风险。同时给予VPA时，卡马西平的主要代谢物卡马西平-10，11-依普赛(CBZ-E)的血浆水平相对于卡马西平的剂量升高，而血浆CBZ水平保持不变。CBZ-E的高血药浓度可能是部分患者出现副作用的原因。药物与蛋白质的相互作用是副作用的另一个来源。卡马西平和丙戊酸联合用药患者的游离或无蛋白血浆CBZ和CBZ-E水平均显著高于单用卡马西平的患者。了解CBZ的药代动力学原理是使用抗癫痫药物治疗儿童的重要基础。

During the past 10 years, better results in the treatment of epilepsy have been obtained through the application of pharmacokinetic data to drug therapy of epilepsy. However, pediatric drug therapy is complicated by the continuous change in body weight and body composition with the growth and development.The plasma levels and seizure control were investigated in a prospective randomized stury when phenytion, carbamazepine (CBz) or sodium valproate (VPA) was given as a single drug to pediatric patients with several types of epileptic seizures. Studies on newly referred, previously untreated children suggest that both partial and generalized tonic-clonic seizured can be prevented by each of the three drugs. No significant differences in clinical efficacy were found between the three drugs, when optimum plasma concentration ranges were maintained with blood level monitoring.Clonazepan (CZP) may be effective in partial seizures. However, as a wide range of plasma levels was associated with complete freedom from seizures, it was not possible to define a therageutic range for CZP.Any patient who receives multiple-drug therapy is at risk to develop a drug-drug interaction. Simultaneous administration of VPA was associated with a raised plasma level of carbamazepine-10,11-eposiex (CBZ-E), a major metabolite of CBZ, relative to the CBZ dose, whereas the plasma CBZ level remained unaltered. The high plasma concentration of CBZ-E may be responsible for the side-effects in some patients.Drug-protein binding interactions are another source of side-effects. The unbound or protein-free plasma levels of both CBZ and CBZ-E in patients treated with CBZ and VPA were significantly higher than those in patients treated with CBZ alone.A working knowledge of the pharmacokinetic principles is an important basis for treating children with antiepileptic drugs.