应用蒙特卡罗模拟法优化中国儿童癫痫患者卡马西平给药方案

Monte Carlo simulation optimizes dosing regimens of carbamazepine for Chinese children with epilepsy

目的应用蒙特卡罗模拟法,结合药动学/药效学理论,优化具有CYP1A2基因多态性特征的中国儿童癫痫患者卡马西平(CBZ)给药方案。方法根据已发表的CBZ在中国儿童癫痫患者中的群体药动学数据,利用蒙特卡罗模拟法预测不同给药方案下,CBZ稳态血药浓度达到有效治疗浓度范围的概率(PTA)。结果当患儿CYP1A2基因型为AA时,CBZ采用8 mg·kg^(-1),tid的给药方案的PTA最大(80.14%);当患儿CYP1A2基因型为CC/CA时,7 mg·kg^(-1),tid的给药方案的PTA最大(80.71%),为最优给药方案;敏感性分析显示,在排除了给药剂量因素后,基因多态性是影响CBZ稳态血药浓度的主要因素。结论通过蒙特卡罗模拟法优化了不同CYP1A2基因型的儿童癫痫患者CBZ给药方案,为临床用药策略的精准化提供了依据。

AIM Using the Monte Carlo simulation(MCS)method in conjunction with pharmacokinetic/pharmacodynamic theory,to optimize the dosing regimen of carbamazepine(CBZ)for Chinese epileptic children with CYPIA2 gene polymorphism.METHODS Based on the published population pharmacokinetic data of CBZ in Chinese children with epilepsy,MCS method was used to predict the probability of target attainment(PTA)of CBZ steady-state blood concentration reaching the effective therapeutic concentration range under different dosing regimens.RESULTS When the CYP1A2 genotype of the pediatric patient was AA,the dosing regimen of CBZ at 8mg·kg^(-1)tid resulted in the highest PTA(80.14%).When the CYP1A2 genotype of the pediatric patient was CC/CA,the dosing regimen of 7 mg·kg^(-1)tid resulted in the highest PTA(80.71%),which was the optimal dosing scheme.Sensitivity analysis showed that after excluding the factor of dosing,genetic polymorphism was the main factor affecting the steady-state plasma concentration of CBZ.CONCLUSION The MCS method has optimized the dosing regimen of CBZ for epileptic children with different CYP1A2 genotypes,providing a basis for precision clinical medic ation strategies.