Dataset Information

Population pharmacokinetics of oxcarbazepine 10-monohydroxy derivative in Chinese adult epileptic patients.

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.

SUBMITTER: Yang Q

PROVIDER: S-EPMC10086726 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Population pharmacokinetics of oxcarbazepine 10-monohydroxy derivative in Chinese adult epileptic patients.

Yang QiaoWei Q Hu Yan Y Zhang XuanLing X Zhang XiaoMin X Dai Haibin H Li Xingang X

European journal of hospital pharmacy : science and practice 20220704 e1

<h4>Objective</h4>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.<h4>Methods</h4>We collected blood samples from Chinese adult epileptic patients taking OXC at the Second Affiliated Hospital of Zhejiang University School of Medicine. We us ...[more]

PMID: 35787526

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Project description:The aim of the present study was to build a population pharmacokinetic (popPK) model to characterize benznidazole (BNZ) pharmacokinetics in adults with chronic Chagas disease. This study was a prospective, open-label, single-center clinical trial approved by the local ethics committee. Patients received BNZ at 2.5 mg/kg of body weight/12 h (Abarax, Elea Laboratory, Argentina) for 60 days. Plasma BNZ samples were taken several times during the study and analyzed by high-performance liquid chromatography with UV-visible detection (HPLC-UV). The popPK analysis was done with NONMEMv.7.3. Demographic and biological data were tested as covariates. Intraindividual, interoccasion, and residual variabilities were modeled. Internal and external validations were completed to assess the robustness of the model. Later on, simulations were performed to generate BNZ concentration-time course profiles for different dosage regimens. A total of 358 plasma BNZ concentrations from 39 patients were included in the analysis. A one-compartment PK model characterized by clearance (CL/F) and the apparent volume of distribution (V/F), with first-order absorption (Ka) and elimination, adequately described the data (CL/F, 1.73 liters/h; V/F, 89.6 liters; and Ka, 1.15 h(-1)). No covariates were found to be significant for CL/F and V/F. Internal and external validations of the final model showed adequate results. Data from simulations revealed that a dose of 2.5 mg/kg/12 h might lead to overexposure in most patients. A lower dose (2.5 mg/kg/24 h) was able to achieve trough BNZ plasma concentrations within the accepted therapeutic range of 3 to 6 mg/liter. In summary, we developed a population PK model for BNZ in adults with chronic Chagas disease. Dosing simulations showed that a BNZ dose of 2.5 mg/kg/24 h will adequately keep BNZ trough plasma concentrations within the recommended target range for the majority of patients. (This study has been registered at EudraCT under number 2011-002900-34 and at ClinicalTrials.gov under number NCT01755403.).

Dataset Information

Population pharmacokinetics of oxcarbazepine 10-monohydroxy derivative in Chinese adult epileptic patients.

Objective

Methods

Result

Conclusion

Trial registration number

Publications

Population pharmacokinetics of oxcarbazepine 10-monohydroxy derivative in Chinese adult epileptic patients.

Similar Datasets

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