Therapeutic drug monitoring · 2025
Population Pharmacokinetic Model of Lacosamide in Chinese Children and Adults with Epilepsy.
СтатьяНазвание и аннотация: Перевод в очереди
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Wu Ruoyun, Liu Shanshan, Zhao Zhigang, Mei Shenghui
Аннотация
OBJECTIVE: To examine the pharmacokinetics of lacosamide (LCM) in Chinese children and adults with epilepsy and to establish a population pharmacokinetic model.
METHODS: A one-compartment model with first-order absorption and elimination was constructed using 482 plasma samples from 391 individuals. Nonlinear mixed-effects modeling accounted for intraindividual and interindividual variabilities. Covariate effects were evaluated through forward inclusion and backward elimination, and the model performance was validated using goodness-of-fit plots and visual predictive checks.
RESULTS: The final population pharmacokinetic (PPK) model indicated that a higher body weight and lower urea levels were associated with increased LCM clearance (CL). Coadministration of phenobarbital or carbamazepine resulted in a 1.42-fold increase in LCM CL. The absorption rate constant was fixed at 0.13, with typical values of CL and apparent volume of distribution (V d ) being 1.19 L/h and 9.95 L, respectively. The association between pharmacokinetic parameters and covariates was quantified as follows: (IND1 = 0.35 if comedicated with phenobarbital or carbamazepine; otherwise = 0).
CONCLUSIONS: The PPK model developed in this study plays a pivotal role in optimizing and personalizing LCM therapy for patients with epilepsy.
METHODS: A one-compartment model with first-order absorption and elimination was constructed using 482 plasma samples from 391 individuals. Nonlinear mixed-effects modeling accounted for intraindividual and interindividual variabilities. Covariate effects were evaluated through forward inclusion and backward elimination, and the model performance was validated using goodness-of-fit plots and visual predictive checks.
RESULTS: The final population pharmacokinetic (PPK) model indicated that a higher body weight and lower urea levels were associated with increased LCM clearance (CL). Coadministration of phenobarbital or carbamazepine resulted in a 1.42-fold increase in LCM CL. The absorption rate constant was fixed at 0.13, with typical values of CL and apparent volume of distribution (V d ) being 1.19 L/h and 9.95 L, respectively. The association between pharmacokinetic parameters and covariates was quantified as follows: (IND1 = 0.35 if comedicated with phenobarbital or carbamazepine; otherwise = 0).
CONCLUSIONS: The PPK model developed in this study plays a pivotal role in optimizing and personalizing LCM therapy for patients with epilepsy.