Banfield C R, Zhu G R, Jen J F, Jensen P K, Schumaker R C, Perhach J L, Affrime M B, Glue P
Department of Clinical Pharmacology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Ther Drug Monit. 1996 Feb;18(1):19-29. doi: 10.1097/00007691-199602000-00004.
The effects of age on felbamate apparent clearance were examined through a retrospective analysis of plasma concentration data from 700 pediatric and adult epileptic patients (age range, 2-74 years) enrolled in six clinical studies. Patients received felbamate as monotherapy or in combination with either the antiepileptic drugs (AEDs) carbamazepine (CBZ), phenytoin (PHT), or valproate (VPA). Data were analyzed using a nonlinear mixed-effects pharmacostatistical modeling technique (NONMEM). Factors in the model included age, body weight, and concomitant AEDs. Apparent clearance was highest in the very young and decreased during the early teenage years, with minimal changes observed beyond 13 years. Mean apparent clearance values were approximately 40% higher in children (2-12 years) compared with those in adults (13-65 years). This pattern and its magnitude were consistent whether felbamate was administered alone or coadministered with CBZ, PHT, or VPA. The increase in clearance is minimal compared with other AEDs including PHT, CBZ, and phenobarbital. Enzyme-inducing AEDs (CBZ and PHT) increased felbamate apparent clearance by 32-38% relative to monotherapy, whereas coadministration with VPA had a minimal effect on felbamate apparent clearance. Dose/concentration linearity was observed at all ages during mono- or polytherapy. These findings suggest that felbamate dosing should be relatively uncomplicated in children relative to that in adults.
通过对参与六项临床研究的700名儿科和成人癫痫患者（年龄范围为2至74岁）的血浆浓度数据进行回顾性分析，研究了年龄对非氨酯表观清除率的影响。患者接受非氨酯单药治疗或与抗癫痫药物（AEDs）卡马西平（CBZ）、苯妥英（PHT）或丙戊酸（VPA）联合使用。使用非线性混合效应药物统计学建模技术（NONMEM）分析数据。模型中的因素包括年龄、体重和同时使用的AEDs。表观清除率在非常年幼的患者中最高，在青少年早期下降，13岁以后变化最小。儿童（2至12岁）的平均表观清除率值比成人（13至65岁）高约40%。无论非氨酯单独使用还是与CBZ、PHT或VPA联合使用，这种模式及其幅度都是一致的。与包括PHT、CBZ和苯巴比妥在内的其他AEDs相比，清除率的增加最小。酶诱导性AEDs（CBZ和PHT）使非氨酯表观清除率相对于单药治疗增加了32%至38%，而与VPA联合使用对非氨酯表观清除率的影响最小。在单药治疗或联合治疗的所有年龄段均观察到剂量/浓度线性关系。这些发现表明，相对于成人，儿童使用非氨酯的给药应该相对简单。
