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Population pharmacokinetics of oxcarbazepine 10-monohydroxy derivative in Chinese adult epileptic patients
  1. QiaoWei Yang1,2,
  2. Yan Hu1,3,
  3. XuanLing Zhang4,
  4. XiaoMin Zhang2,
  5. Haibin Dai1,
  6. Xingang Li4
  1. 1Department of Pharmacy, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, Zhejiang, China
  2. 2Department of Pharmacy, Sanmen People’s Hospital, Taizhou, Zhejiang Province, People's Republic of China
  3. 3Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People's Republic of China
  4. 4Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, Beijing, China
  1. Correspondence to Dr Haibin Dai, Department of Pharmacy, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, People's Republic of China; haibindai{at}zju.edu.cn; Dr Xingang Li, Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China; lxg198320022003{at}163.com

Abstract

Objective Oxcarbazepine (OXC) is metabolised to active 10-monohydroxy derivative (MHD) after oral administration. Using this fact we aimed to develop an MHD population pharmacokinetic (PPK) model in Chinese adult epileptic patients to facilitate the clinical implementation of model-guided individualised drug therapy.

Methods We collected blood samples from Chinese adult epileptic patients taking OXC at the Second Affiliated Hospital of Zhejiang University School of Medicine. We used high performance liquid chromatography (HPLC-MS/MS) with tandem mass spectrometry to detect MHD concentrations in the blood samples. We collected various data from patients including their demographic, pathological, and physiological information. MassARRAY method was used to detect ABCC2, ABCB1, SCN8A, SCN1A, SCN2A, SCN3A, UGT1A9, and UGT2B7 gene polymorphisms. We used a nonlinear mixed-effects modelling method to develop the PPK model and we predicted dosing regimens through simulation.

Result In total we collected 164 blood samples from 118 patients. We found that a one-compartment model with first-order absorption better described the in vivo MHD pharmacokinetics. UGT2B7 gene (rs7439366) site mutation and the combined use of valproic acid enhanced the MHD clearance rate. We divided patients into groups based on the UGT2B7 genotype and whether they were also using valproic acid at the same time. Individualised OXC dosing regimens were proposed for different subgroups of patients.

Conclusion In Chinese adult epileptic patients, individualised drug administration can be facilitated using a PPK model of OXC.

Trial registration number ChiCTR-OOC-17012141.

  • chemistry, clinical
  • drug monitoring
  • pharmacy service, hospital
  • pharmacology
  • neurology

Data availability statement

Data are available upon reasonable request. Data can be shared with the approval of relevant agencies.

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Data availability statement

Data are available upon reasonable request. Data can be shared with the approval of relevant agencies.

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