基于蒙特卡洛模拟优化中国癫痫患儿左乙拉西坦给药方案

Optimization of levetiracetam maintenance regimen in Chinese epileptic children based upon Monte Carlo simulation

目的:基于蒙特卡洛模拟(Monte Carlo simulation,MCS)优化中国癫痫患儿的左乙拉西坦(levetiracetam,LEV)维持给药方案。方法:根据已发表的中国癫痫患儿LEV群体药动学数据,使用MCS预测LEV在不同给药方案下稳态血药浓度(C_(ss))以及其处于目标浓度范围10~40、0~10、10~20、20~30以及30~40 mg·L^(-1)的概率分布。结果:对于0~17岁癫痫患儿使用LEV进行治疗,采用15 mg·kg^(-1)bid的维持给药方案时,Css分布于10~40 mg·L^(-1)的PTA值最大(为97.4%),当目标浓度为0~10 mg·L^(-1)时,患儿采用5 mg·kg^(-1)bid的给药方案时,PTA值最大(为69.3%),当目标浓度为10~20 mg·L^(-1)时,采用8 mg·kg^(-1)bid的给药方案时,PTA值最大(为66%),设置目标浓度范围为20~30 mg·L^(-1)时,患儿采用12.5 mg·kg^(-1)bid的给药方案时,PTA值最大(为43.5%),置目标浓度范围为30~40 mg·L^(-1)时,患儿采用17.5 mg·kg^(-1)bid的给药方案时,PTA值最大(为31.1%)。结论:研究应用MCS模拟预测了中国癫痫患儿给予不同LEV维持剂量下的C_(ss)及分布于不同参考浓度范围的达标概率,可以为LEV给药方案优化提供参考。

OBJECTIVE To optimize maintenance regimen of levetiracetam(LEV)in Chinese epileptic children based upon Monte Carlo simulation(MCS).METHODS According to the published pharmacokinetic data of LEV population in Chinese epileptic children,MCS was utilized for predicting the steady-state blood concentration(C_(ss))of LEV under different dosing regimens and the probability distribution of Css within the therapeutic concentration reference range of 10 to 40 mg·L^(-1).RESULTS For LEV dosing in epileptic children aged 0–17 years,the maximal PTA value(97.4%)of Css distributed in 10–40 mg·L^(-1)was obtained with a dose of Lev at 15 mg·kg^(-1)bid.At a target concentration of 0–10 mg·L^(-1),PTA value peaked(69.3%)at a dose of 5 mg·kg^(-1)bid;at a target concentration of 10–20 mg·L^(-1),maximal PTA value was 66%at a dose of 8 mg·kg^(-1)bid;at a target concentration of 20–30 mg·L^(-1),PTA value peaked(43.5%)with a dose of 12.5 mg·kg^(-1)bid;at a target concentration of 30–40 mg·L^(-1),PTA value peaked(31.1%)at a dose of 17.5 mg·kg^(-1)bid.CONCLUSION MCS simulation may predict the reaching probability of C_(ss)at different LEV maintenance doses and reveal its distribution in different reference concentration ranges in Chinese epileptic children.It provides references for optimizing LEV dosing regimen.