Population pharmacokinetics of oxcarbazepine in Chinese epilepsy patients
10.16438/j.0513-4870.2018-0187
- VernacularTitle:奥卡西平在癫痫患者中的群体药动学研究
- Author:
Meng LIU
1
;
Chun-lai MA
2
;
Zheng JIAO
2
;
Yu-cheng GAO
2
;
Yi-xi LIU
2
;
Xun-yi WU
3
Author Information
1. Department of Pharmacy, Lu'an Hospital of Traditional Chinese Medicine, Lu'an 237006, China
2. Department of Pharmacy, Fudan University, Shanghai 200040, China
3. Department of Neuology, Huashan Hospital, Fudan University, Shanghai 200040, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
epilepsy;
oxcarbazepine;
10-hydroxycarbazepine;
population pharmacokinetics;
nonlinear mixed effect model;
individualized therapy
- From:
Acta Pharmaceutica Sinica
2018;53(8):1318-1323
- CountryChina
- Language:Chinese
-
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=1.84×0.848UGT2B7×1.17GENDER. 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.
