Plasma Levels and Clinical Pharmacology of Antiepileptic Drugs in Children

近10年来，将药代动力学数据应用于癫痫的药物治疗，取得了较好的治疗效果。然而，随着儿童的生长发育，体重和身体成分的不断变化，使儿童药物治疗变得复杂。在一项前瞻性随机研究中，当phenytion、卡马西平（CBz）或丙戊酸钠（VPA）作为单一药物给药给患有几种类型癫痫发作的儿科患者时，研究了血浆水平和癫痫发作控制。对新转诊，以前未治疗的儿童的研究表明，部分和全身性强直阵挛发作可以通过这三种药物中的每一种来预防。在维持最佳血药浓度范围并监测血药浓度的情况下，三种药物的临床疗效无显著差异。氯硝安定（CZP）可能对部分性癫痫发作有效。然而，由于广泛的血浆水平与完全免于癫痫发作有关，因此不可能确定CZP的治疗范围。任何接受多种药物治疗的病人都有发生药物相互作用的风险。同时给予VPA与卡马西平-10,11-eposiex （CBZ的主要代谢物）的血浆水平相对于CBZ剂量升高相关，而血浆CBZ水平保持不变。在一些患者中，高血浆浓度的CBZ-E可能是副作用的原因。药物-蛋白质结合相互作用是副作用的另一个来源。联合使用CBZ和VPA治疗的患者血浆中CBZ和CBZ- e的未结合或游离蛋白水平明显高于单独使用CBZ治疗的患者。药物动力学原理的工作知识是治疗儿童抗癫痫药物的重要基础。

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.