Pharmacokinetics of Carbamazepine in Chinese Patients with Epilepsy: A Population Pharmacokinetic Analysis
Authors: Y. Zhang, L. Wang, H. Li, J. Chen, X. Liu
Background and Objective: Carbamazepine (CBZ) is a first-line antiepileptic drug with narrow therapeutic index and high interindividual variability. This study aimed to develop a population pharmacokinetic (PopPK) model of CBZ in Chinese patients with epilepsy and to identify factors affecting its disposition. Methods: A prospective study was conducted in 120 Chinese patients with epilepsy receiving CBZ monotherapy. Blood samples were collected at steady state, and CBZ concentrations were measured using a validated HPLC method. Population pharmacokinetic analysis was performed using NONMEM 7.4. Covariate analysis included demographic, clinical, and genetic factors (CYP3A4*1B, CYP3A5*3, ABCB1 C3435T). Results: A one-compartment model with first-order absorption and elimination adequately described the data. Typical values of apparent clearance (CL/F) and volume of distribution (V/F) were 3.42 L/h and 1.12 L/kg, respectively. Significant covariates included body weight, age, and CYP3A5*3 genotype. CL/F increased with body weight and decreased with age; CYP3A5*3 carriers had 20% lower CL/F compared to non-carriers. Interindividual variability in CL/F was 28.5%. Model evaluation via bootstrap and visual predictive check confirmed stability and predictive performance. Conclusions: A PopPK model of CBZ in Chinese epileptic patients was successfully developed. Body weight, age, and CYP3A5*3 genotype significantly influence CBZ clearance, which may guide individualized dosing. Further studies are warranted to validate the model in larger populations and explore other genetic variants.
