应用蒙特卡罗模拟评价和优化第三代抗癫痫药物拉考沙胺的儿童给药方案  

Application of Monte Carlo Simulation to Evaluate and Optimize the Pediatric Dosage Regimen of the Third-Generation Antiepileptic Drug Lacosamide

作　　者：万雄飞 廖念 朱珊珊 汪洋[2] 梁美锋 Wan Xiongfei;Liao Nian;Zhu Shanshan;Wang Yang;Liang Meifeng(China Resources&Wuhan Iron and Steel(Group)Company General Hospital Affiliated to Wuhan University of Science and Technology,Wuhan430080,China;Wuhan Children’s Hospital,Tongji Medical College,Huazhong University of Science&Technology,Wuhan 430016,China)

机构地区：[1]武汉科技大学附属华润武钢总医院,武汉430080 [2]华中科技大学同济医学院附属武汉儿童医院,武汉430016

出　　处：《儿科药学杂志》2025年第3期1-5,共5页Journal of Pediatric Pharmacy

摘　　要：目的:评价和优化拉考沙胺(LCM)治疗儿童癫痫的给药方案,促进个体化用药。方法:基于已公开发表的LCM治疗儿童癫痫的药动学/药效学(PK/PD)参数,采用蒙特卡罗模拟(MCS)计算不同体质量及联合用药特征分层患者口服不同剂量LCM后的血浆稳态谷浓度(C_(0))。根据C_(0)相对于目标谷浓度范围(2~7 mg/L)的达标概率(PTA)来评价不同LCM维持剂量方案的合理性。采用模拟试验评估儿童癫痫患者在发生不同漏服场景下的LCM谷浓度脱靶情况并建立适宜的补救方案。结果:儿童癫痫患者按本研究推荐的LCM维持剂量方案和漏服补救剂量方案给药后可使C_(0)达到目标浓度范围下限的PTA≥75%,且高于上限的概率较低。模拟试验结果显示,为达到同等的体内药物暴露水平,体质量较轻的儿童患者应该给予较高的体质量校正剂量,而联用酶诱导剂时LCM的剂量应提高至单药治疗时的1.5~2.3倍。结论:本研究采用MCS优化了不同体质量及联合用药特征分层儿童患者的维持剂量方案,同时建立了漏服药物后的补救方案,可为LCM临床个体化用药提供参考。Objective:To evaluate and optimize the dosage regimen of lacosamide(LCM)for the treatment of epilepsy in children,and promote individualized medication.Methods:Based on the published pharmacokinetic/pharmacodynamic(PK/PD)parameters of LCM in children with epilepsy,Monte Carlo simulation(MCS)was used to calculate the steady-state trough plasma concentration(C_(0))after oral administration of different doses of LCM in patients stratified by body weight and co-medication characteristics.The rationality of different LCM maintenance dose regimens was evaluated based on the probability of target concentration(PTA)of C_(0)relative to the target range of 2 to 7 mg/L.And simulation tests were employed to assess the off-target situation of LCM trough concentration in children with epilepsy under different scenarios of missed doses and to establish appropriate remedial regimens.Results:The probability of achieving the lower limit of the target concentration range for C_(0)in children with epilepsy after administration of LCM maintenance dose regimens and remedial dose regimens recommended in this study was⩾75%,and the probability of exceeding the upper limit was low.Simulation results showed that in order to achieve the same level of in vivo drug exposure,children with low body weight should be given a higher weight correction dose,and the dose of LCM in combination with enzyme inducers should be increased to 1.5 to 2.3 times that of monotherapy.Conclusion:In this study,MCS is used to optimize the maintenance dose regimens for stratified children with different body weight and co-medication characteristics,and to establish the remedial dose regimens after missing medication,which can provide reference for clinical individualized medication of LCM.

关 键 词：蒙特卡罗模拟 拉考沙胺 儿童 癫痫 个体化用药 

分 类 号：R917[医药卫生—药物分析学]