目的 根据药动/药效理论应用蒙特卡洛模拟(Monte Carlo simulation,MCS)优化中国癫痫患者卡马西平(Carbamazepine,CBZ)的维持给药方案.方法 基于已发表的中国癫痫患者CBZ的群体药动学参数,通过MCS模拟10000例次,比较CBZ的22种给药方案可能达到的稳态血药浓度(Css)及落在不同目标浓度范围的概率(Probability of target attainment,PTA).结果 当目标浓度范围为4～8 mg·L-1,对于年龄＜65岁患者,CBZ 100 mg,tid的给药方案下PTA最大;年龄＞65岁患者,100 mg,bid的给药方案下PTA最大.当目标浓度范围为8～12 mg·L-1,对于年龄＜65岁患者,CBZ 300 mg,tid的给药方案下PTA最大,年龄＞65岁患者,200 mg,tid的给药方案下PTA最大.结论 MCS可预测中国癫痫患者予不同CBZ给药方案下Css分布于不同目标浓度范围的达标概率,为CBZ给药方案优化提供参考.
Application of Monte Carlo Simulation to Optimize the Administration Plan of Carbamazepine in Chinese Epilepsy Patients
OBJECTIVE Based on pharmacokinetic/pharmacodynamic theory,Monte Carlo simulation(MCS)is applied to optimize the maintenance dosing regimen of carbamazepine(CBZ)in Chinese epilepsy pa-tients.METHODS Based on the published population pharmacokinetic parameters of CBZ in Chinese epileptic pa-tients,a Monte Carlo Simulation of 10,000 iterations was conducted to compare the potential steady-state blood con-centrations(Css)and the probabilities of target attainment(PTA)within different target concentration ranges for 22 dosing regimens of CBZ.RESULTS When the target concentration range is 4-8 mg·L-1,the dosing regimen of CBZ 100 mg,tid results in the highest PTA for patients younger than 65 years old,while the dosing regimen of 100 mg,bid achieves the highest PTA for patients older than 65 years old.When the target concentration range is 8-12 mg·L-1,the dosing regimen of CBZ 300 mg,tid leads to the highest PTA for patients younger than 65 years old,and the dosing regimen of 200 mg,tid results in the highest PTA for patients older than 65 years old.CONCLUSION MCS can predict the probability of Css distribution within different target concentration ranges for Chinese epileptic patients under various CBZ dosing regimens,providing a reference for optimizing CBZ dosing strategies.
CarbamazepineMonte carlo simulationEpilepsyDose optimization
万方数据
维普
