PDF(Pubmed)
Abstract：
The purposes of this study were to explore the population pharmacokinetics and initial dose optimization of sirolimus improving drug blood level for seizure control in pediatric patients with tuberous sclerosis complex (TSC). Eighty pediatric patients diagnosed with TSC-related epilepsy were included for analysis. Sirolimus concentrations, physiological and biochemical indexes, and drug combination were collected to build a nonlinear mixed effect (NONMEM) model. Initial dose optimization was simulated by the Monte Carlo method. The weight and concomitant medication of oxcarbazepine affected sirolimus clearance. Without oxcarbazepine, for once-daily sirolimus regimen, the doses of 0.07, 0.06, 0.05, 0.04, and 0.03 mg/kg/day were recommended for weights of 5-7.5, 7.5-11.5, 11.5-19, 19-40, and 40-70 kg, respectively; for twice-daily sirolimus regimen, the doses of 0.05, 0.04, and 0.03 were recommended for weights of 5-8, 8-20, and 20-70 kg, respectively. With oxcarbazepine, for once-daily sirolimus regimen, the doses of 0.09, 0.08, 0.07, 0.06, 0.05, and 0.04 mg/kg/day were recommended for weights of 5-7.5, 7.5-10, 10-13.5, 13.5-20, 20-35, and 35-70 kg, respectively; for twice-daily sirolimus regimen, the doses of 0.06, 0.05, 0.04, and 0.03 were recommended for weights of 5-7, 7-14.5, 14.5-38, and 38-70 kg, respectively. The present study was the first to establish a population pharmacokinetic model of sirolimus improving drug blood level for seizure control in pediatric patients with TSC and recommend the initial dosage regimen.
摘要：
这项研究的目的是探索西罗莫司的群体药代动力学和初始剂量优化，以改善患有结节性硬化症（TSC）的小儿患者的癫痫发作控制药物血液水平。纳入80例诊断为TSC相关癫痫的儿科患者进行分析。西罗莫司浓度,生理生化指标,和药物组合收集建立非线性混合效应(NONMEM)模型。通过蒙特卡罗方法模拟初始剂量优化。奥卡西平的体重和合并用药会影响西罗莫司的清除率。没有奥卡西平,对于每日一次的西罗莫司方案，建议体重为5-7.5、7.5-11.5、11.5-19、19-40和40-70kg的剂量为0.07、0.06、0.05、0.04和0.03mg/kg/天，分别是每日两次西罗莫司方案，体重为5-8、8-20和20-70公斤时，推荐剂量为0.05、0.04和0.03，分别。用奥卡西平,对于每日一次的西罗莫司方案，建议体重为5-7.5、7.5-10、10-13.5、13.5-20、20-35和35-70公斤的剂量为0.09、0.08、0.07、0.06、0.05和0.04毫克/公斤/天，分别是每日两次西罗莫司方案，体重为5-7、7-14.5、14.5-38和38-70公斤时，建议使用0.06、0.05、0.04和0.03的剂量，分别。本研究首次建立了西罗莫司改善药物血液水平的群体药代动力学模型，以控制TSC患儿的癫痫发作，并推荐了初始给药方案。
