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Influence of UDP-glucuronosyltransferase polymorphisms on valproic acid pharmacokinetics in Chinese epilepsy patients

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to investigate the genetic polymorphisms of UGT1A3, UGT1A6, and UGT2B7 in Chinese epilepsy patients and their potential influence on the pharmacokinetics of valproic acid (VPA).

Methods

The genetic architectures of UGT1A3, UGT1A6, and UGT2B7 in 242 epilepsy patients were detected by DNA sequencing and PCR-restriction fragment length polymorphism. Steady-state plasma concentrations of VPA in 225 patients who had received VPA (approx. 250–1,000 mg/day) for at least 2 weeks were determined and associated with UGT polymorphisms.

Results

The allelic distribution of UGT1A3 in our Chinese epilepsy patients was significantly different from that in healthy subjects based on reference data. The standardized trough plasma concentration (CS) of VPA was much lower in our patients with the UGT1A3*5 variant than in the wild type carriers (3.24 ± 1.05 vs. 4.68 ± 1.24 μg·kg·mL-1·mg-1, P < 0.01). UGT polymorphisms had no influence on the pharmacokinetic interactions between carbamazepine and VPA.

Conclusion

Our results suggest that UGT1A3*5 may be an important determinant of individual variability in the pharmacokinetics of VPA and that it may be necessary to increase VPA dose for UGT1A3*5 carriers to ensure its therapeutic range of 50–100 μg/mL.

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Funding

This work was supported by the National Natural Science Foundation (Grants 91029746, 81072695), Jiangshu province Natural Science Foundation (Grant BK 2010066), and a funding for innovative research team in institutions of Jiangsu higher education.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, Jinling Hospital, Nanjing, China

    Xiao-Man Chu & Jia-Hui Zhou

  2. State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, No. 24, Tongjiaxiang Street, Nanjing, 210009, China

    Li-Fang Zhang, Guang-Ji Wang & Hai-Ping Hao

  3. Department of Neurology, Jinling Hospital, Nanjing, China

    Shen-Ning Zhang

Authors
  1. Xiao-Man Chu
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  2. Li-Fang Zhang
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  3. Guang-Ji Wang
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  4. Shen-Ning Zhang
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Corresponding author

Correspondence to Hai-Ping Hao.

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Xiao-Man Chu and Li-Fang Zhang contributed equally to this work.

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Chu, XM., Zhang, LF., Wang, GJ. et al. Influence of UDP-glucuronosyltransferase polymorphisms on valproic acid pharmacokinetics in Chinese epilepsy patients. Eur J Clin Pharmacol 68, 1395–1401 (2012). https://doi.org/10.1007/s00228-012-1277-7

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  • DOI: https://doi.org/10.1007/s00228-012-1277-7

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