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Population pharmacokinetic modeling of oxcarbazepine active metabolite in Chinese patients with epilepsy

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An Erratum to this article was published on 14 October 2016

Abstract

The aim of the study was to develop a population pharmacokinetic (PPK) model of oxcarbazepine and optimize the treatment of oxcarbazepine in Chinese patients with epilepsy. A total of 108 oxcarbazepine therapeutic drug monitoring samples from 78 patients with epilepsy were collected in this study. The pharmacologically active metabolite 10,11-dihydro-10-hydrocarbamazepine (MHD) was used as the analytical target for monitoring therapy of oxcarbazepine. Patients’ clinical data were retrospectively collected. The PPK model for MHD was developed using Phoenix NLME 1.2 with a non-linear mixed-effect model. MHD pharmacokinetics obeys a one-compartment model with first-order absorption and elimination. The effect of age, gender, red blood cell count, red blood cell specific volume, hemoglobin (HGB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatine were analyzed. Bootstrap and data splitting were used simultaneously to validate the final PPK models. The mean values of volume of distribution and clearance of MHD in the patients were 14.2 L and 2.38 L h−1, respectively. BUN and HGB influenced the MHD volume of distribution according to the following equation: V = tvV × (BUN/4.76)−0.007 × (HGB/140)−0.001 × eηV. The MHD clearance was dependent on ALT and gender as follows: CL = tvCL × (ALT/30)0.181 × (gender) × 1.083 × eηCL. The final PPK model was demonstrated to be suitable and effective and it can be used to evaluate the pharmacokinetic parameters of MHD in Chinese patients with epilepsy and to choose an optimal dosage regimen of oxcarbazepine on the basis of these parameters.

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Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

BUN:

Blood urea nitrogen

Cr:

Serum creatine

EIAEDs:

Enzyme-inducing antiepileptic drugs

HCT:

Red blood cell specific volume

HGB:

Hemoglobin

IPRED:

Individual predicted value

MHD:

10,11-Dihydro-10-hydrocarbamazepine

PRED:

Predicted value

RBC:

Red blood cell counts

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Acknowledgments

This work was supported by the Pharmaceutical foundation of Suzhou (No. SYSD2012129 and SYSD2013144).

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People’s Republic of China

    Yunli Yu, Quanying Zhang & Wenjun Xu

  2. Department of Pharmaceutics, Soochow University Affiliated Children’s Hospital, Suzhou, 215003, People’s Republic of China

    Chengzhe Lv

  3. Suzhou Institute for Food and Drug Control, Suzhou, 215104, People’s Republic of China

    Gang Hao

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  1. Yunli Yu
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  2. Quanying Zhang
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  3. Wenjun Xu
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  4. Chengzhe Lv
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Corresponding author

Correspondence to Yunli Yu.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s13318-016-0379-5.

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Yu, Y., Zhang, Q., Xu, W. et al. Population pharmacokinetic modeling of oxcarbazepine active metabolite in Chinese patients with epilepsy. Eur J Drug Metab Pharmacokinet 41, 345–351 (2016). https://doi.org/10.1007/s13318-015-0266-5

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  • DOI: https://doi.org/10.1007/s13318-015-0266-5

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