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. 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. The weight and concomitant medication of oxcarbazepine affected sirolimus clearance. Initial dose optimization was simulated by the Monte Carlo method. Sirolimus concentrations, physiological and biochemical indexes, and drug combination were collected to build a nonlinear mixed effect (NONMEM) model. Eighty pediatric patients diagnosed with TSC-related epilepsy were included for analysis. 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). 3Department of Neurology, Children’s Hospital of Fudan University, Shanghai, China.2Department of Nephrology, Children’s Hospital of Fudan University, Shanghai, China.1Department of Pharmacy, Children’s Hospital of Fudan University, Shanghai, China.Xiao Chen 1 †, Dongdong Wang 1 †, Lin Zhu 1, Jinmiao Lu 1, Yidie Huang 1, Guangfei Wang 1, Yiqing Zhu 1, Qiaofeng Ye 1, Yi Wang 3*, Hong Xu 2* and Zhiping Li 1*

Nonmem weighted optimization