Population pharmacokinetics of oxcarbazepine active metabolite in Chinese paediatric patients with epilepsy: Model-based dose optimization.

Autor: Wu W; Department of Clinical Pharmacy, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China., Yang WS; Department of Clinical Pharmacy, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China., Xu XY; Department of Clinical Pharmacy, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China., Ge XL; Department of Clinical Pharmacy, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China., Lu J; Department of Clinical Pharmacy, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China., Wang GF; Department of Clinical Pharmacy, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China., Wang Y; Department of Neurology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China., Li ZP; Department of Clinical Pharmacy, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Jazyk: angličtina
Zdroj: Basic & clinical pharmacology & toxicology [Basic Clin Pharmacol Toxicol] 2024 May; Vol. 134 (5), pp. 712-726. Date of Electronic Publication: 2024 Mar 20.
DOI: 10.1111/bcpt.14000
Abstrakt: The pharmacological activity of oxcarbazepine (OXC) is primarily exerted through its active 10-monohydroxy metabolite (MHD). Nonetheless, there is limited pharmacokinetic information available regarding paediatric patients with epilepsy treated with OXC, especially in infants and toddlers. Concurrently, this drug exhibits substantial variability in pharmacokinetics and therapeutic response across different individuals. We aimed to develop a model to quantitatively investigate factors that affect MHD pharmacokinetics to formulate a dosage guideline for OXC in Chinese paediatric patients. A total of 297 MHD trough concentrations were obtained from 287 epileptic children. Six body weight (BW)-based allometric models were used for population pharmacokinetic modelling, while investigating the impact of other covariates on the apparent clearance. The one-compartment model and age cut-off model for the apparent clearance (CL/F) were established to describe the pharmacokinetics of MHD. The probability to obtain target trough concentration ranges (TTCRs) of MHD between 3 and 35 mg/L was determined by Monte Carlo simulations for doses ranging from 8 to 90 mg/kg/day. A new dose optimization strategy combining the dosage guidelines and Bayesian method provides a tailored approach for Chinese paediatric epileptic patients based on their individual BW and desired TTCRs of MHD, and also supports current dose recommendations, with the exception of children weighing ≤5 kg.
(© 2024 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)
Databáze: MEDLINE
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