External Validation and Precision Drug Use of Pharmacokinetic Model of Lacosamide in Foreign Pediatric Populations
Objective To verify the predictive performance of the population pharmacokinetic(PPK)model of lacosamide in children reported abroad using real-world case data,the exposure-response relationship was analyzed,and the optimal dosing regimen was simulated.Methods The plasma concentration data and clinical data of 64 children with epilepsy aged 4-13.42 years after oral administration of lacosamide reached a steady state were collected,and the prediction accuracy of foreign models was investigated by goodness-of-fit diagram and intuitive prediction test.The relationship between the daily dose or trough concentration of lacosamide and the clinical efficacy was analyzed,and Monte Carlo simulation was used to evaluate and screen the optimal dosing regimen of lacosamide for different body weight stratification and combinations based on pharmacokinetic parameters.Results The external validation results show that the prediction accuracy of the PPK model for children abroad is good.The pharmacokinetic parameters of lacosamide monotherapy in children with epilepsy were as follows:absorption rate constant(ka)=(2.43±0.04)h-1,apparent volume of distribution(Vd/F)=(22.69±6.00)L,clearance rate(CL/F)=(1.25±0.27)L·h-1,half-life(t1/2)=(12.74±2.40)h.The distribution range of 5％-95％quantile of daily dose of clinically effective cases was 2.5-6.3 mg·kg-1·d-1,and the distribution range of 5％-95％of trough concentration was 1.9-6.7 mg·L-1.The simulation results showed that the optimized dosing regimen of lacosamide recommended in this study could increase the probability of drug concentration reaching the target and ensure the efficacy and tolerability of treatment.Conclusions The prediction performance of the PPK model of lacosamide in foreign children was verified,and the optimal dosing regimen was simulated based on this model,which can provide a reference for clinicians to individualize and rationalize the use of drugs.
万方数据
维普
