儿童和青少年癫痫治疗期间卡马西平与某些抗癫痫药物的药代动力学相互作用。

Pharmacokinetic interactions of carbamazepine with some antiepileptic drugs during epilepsy treatment in children and adolescents.

作者信息

Steinborn B

机构信息

Department of Developmental Neurology, K. Marcinkowski University of Medical Sciences, Poznań, Poland.

出版信息

Rocz Akad Med Bialymst. 2005;50 Suppl 1:9-15.

PMID:16119616

Abstract

PURPOSE

The aim of the study was to obtain pharmacokinetic data for carbamazepine (CBZ) and its fractions not bound with proteins in bitherapy with lamotrigine (LTG), topiramate (TPM), vigabatrin (VGB) or valproic acid (VPA) in children and adolescents treated for epilepsy.

MATERIAL AND METHODS

The participants of the presented investigations were fifty-five patients with epilepsy who were under control of The Department of Developmental Neurology, University of Medical Sciences in Poznaf. All of patients were treated with CBZ in bitherapy with LTG, TPM, VGB or VPA. The blood samples were taken under steady-state conditions, before the morning dose and subsequently every 3 or 2 for 24 h. The plasma levels of CBZ were determined using TDX analyzer (Abbott Diagnostic Division, USA). Free CBZ fraction was isolated with the use of ultrafiltration system (Amicon, USA). For pharmacokinetic calculations of total and free CBZ, one-compartment model was used according to standardized procedure.

RESULTS

No significant differences in pharmacokinetic parameters of unbound CBZ in four groups of patients on bitherapy with CBZ and LTG, TPM, VGB or VPA were found. The changes in pharmacokinetics of total CBZ were related with difference in CBZ concentrations, area under curve (AUC), L/D/kg ratios and clearance (Cl)/kg. CBZ+VGB bitherapy led to higher total CBZ concentrations. In the group on bitherapy with CBZ+VPA, no increase in unbound CBZ was detected.

CONCLUSIONS

Pharmacokinetic interactions of CBZ with LTG, TPM, VGB or VPA in children are associated only with the changes in total CBZ parameters.

摘要

目的

本研究旨在获取在接受癫痫治疗的儿童和青少年中，卡马西平（CBZ）及其与拉莫三嗪（LTG）、托吡酯（TPM）、氨己烯酸（VGB）或丙戊酸（VPA）联合治疗时未与蛋白质结合部分的药代动力学数据。

材料与方法

本研究的参与者为55例癫痫患者，他们由波兹南医科大学发育神经学系负责管理。所有患者均接受CBZ与LTG、TPM、VGB或VPA联合治疗。在稳态条件下，于晨服药物前采集血样，随后每3小时或2小时采集一次，共采集24小时。使用TDX分析仪（美国雅培诊断部）测定血浆中CBZ的水平。使用超滤系统（美国密理博公司）分离游离CBZ部分。对于总CBZ和游离CBZ的药代动力学计算，根据标准化程序采用一室模型。

结果

在接受CBZ与LTG、TPM、VGB或VPA联合治疗的四组患者中，未结合CBZ的药代动力学参数未发现显著差异。总CBZ药代动力学的变化与CBZ浓度、曲线下面积（AUC）、L/D/kg比值和清除率（Cl）/kg的差异有关。CBZ + VGB联合治疗导致总CBZ浓度更高。在CBZ + VPA联合治疗组中，未检测到游离CBZ增加。