Abstract:
Oxcarbazepine (OXC) is a common antiepileptic drugs. In this study, one hundred and eighty four epilepsy patients with 196 observations of oxcarbazepine's active metabolite, 10,11-dihydro-10-monohydroxy carbazepine (MHD) were collected prospectively from routine clinical monitoring. Nonlinear mixed effect modeling was employed to develop a population pharmacokinetic model of oxcarbazepine in Chinese patients with epilepsy to investigate the impact of gender, age, weight, co-medications and genetic polymorphisms of
UGT2B7 c.802T>
C,
ABCC2 c.1249G>
A,
ABCC 23972C>
T on pharmacokinetic characteristics of OXC. The population estimate of apparent clearance (CL
/F) and apparent volume of distribution (
V/F) was 1.84 L·h
−1 and 275 L, respectively. Gender and
UGT2B7 c.802T>
C affected the clearance rate of MHD significantly. The established model was:CL/
F=1.84×0.848
UGT2B7×1.17
GENDER. Where the genotype of
UGT2B7 c.802T>
C was
CC,
UGT2B7=0, otherwise
UGT2B7=1. When the patient was male, GENDER=1, otherwise GENDER=0. The final model was evaluated by normalized predictive distribution error (NPDE) and bootstrap method. The model was stable and reliable, which offers a powerful approach for rational use of OXC in epilepsy patients.