中国成年癫痫患者奥卡西平活性代谢产物的群体药动学

Population pharmacokinetics of the active metabolite of oxcarbazepine in Chinese patients with epilepsy

目的:建立中国癫痫患者奥卡西平活性代谢产物10-羟基卡马西平的群体药动学模型,进而取得对癫痫患者有效的数据参数,为癫痫患者给出有针对性的给药治疗依据。方法:通过实地收集参与研究使用奥卡西平片患者血液药物含量监测数据,利用NLME软件来实现近似群体药动学数学逻辑模型,建立基础模型和统计学模型后,考察年龄、体质量、合并用药等潜在影响10-羟基卡马西平药动学的相关变量参数,将Bootstrap估得的和原始数据估得的参数值进行对比分析,确保模型对实验有效以及测验结果稳定,对建立的模型通过自举法进行验证。结果:共收集了119个患者的180个浓度点,所建立的10-羟基卡马西平的群体药动学模型符合一级吸收、一级消除的一室模型,CL/F及V_d/F群体值分别为1.22 L·h^(-1)和43.21 L;K_a固定为0.5 h^(-1)。体表面积对10-羟基卡马西平的清除率有显著影响。结论:初步建立了中国癫痫患者奥卡西平活性代谢产物10-羟基卡马西平的群体药动学模型,为癫痫患者给出了有针对性的给药治疗依据。

OBJECTIVE To establish the population pharmacokinetics model of 10-hydroxy carbamazepine,the active metabolite of oxcarbazepine,in Chinese epileptic patients,to obtain the data and parameters effective for epileptic patients.M ETHODS By collecting monitoring data of blood drug contents in patients receiving oxcarbazepine,utilizing NLME software to establish the mathematical logic model of approximate population pharmacokinetics,basic model and statistical model were constructed to investigate relevant variables and parameters related with pharmacokinetics of 1 0-hydroxy carbamazepine,including age,body weight,combined drugs,etc. Estimate values by bootstrap and original data were compared to ensure the models were effective for the experiment,the test results were stable,and the constructed models would be validated by using bootstrap method. RESULTS Totally 1 8 0 concentrations were collected from 1 1 9 patients. The established population pharmacokinetics model of 1 0-hydroxy carbamazepine fit one compartmental model of first order absorption and first order elimination. The population values of CL/F and Vd/F were 1. 2 2 L·h^-1 and 4 3. 2 1 L,respectively; Kavalue was fixed as0. 5 h^-1. CONCLUSION The study preliminarily establishes the population pharmacokinetics model of 1 0-hydroxy carbamazepine,the active metabolite of oxcarbazepine,in Chinese epileptic patients,and provides a reference for drug therapy oriented to epileptic patients.