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BMC Genomics

Open Access

Pharmacogenetics of uridine diphosphate glucuronosyltransferase (UGT2B7) genetic polymorphism on valproic acid pharmacokinetics in epilepsy

  • Murali Munisamy1Email author,
  • Gauthaman Karunakaran2,
  • Mubarak Al-Gahtany3,
  • Vivekanandhan Subbiah4 and
  • Manjari M Tripathi4
BMC Genomics201415(Suppl 2):P3

https://doi.org/10.1186/1471-2164-15-S2-P3

Published: 2 April 2014

Background

Sodium valproate is a widely prescribed broad-spectrum antiepileptic drug. It shows high inter-individual variability in pharmacokinetics and pharmacodynamics and has a narrow therapeutic range [1]. We evaluated the effects of polymorphic Uridine diphosphate glucuronosyltransferase (UGT2B7) metabolizing enzyme on the pharmacokinetics of sodium valproate in the patients with epilepsy who showed toxicity to therapy.

Materials and methods

Genotype analysis of the patients was made with polymerase chain–restriction fragment length polymorphism (RFLP) with sequencing. Plasma drug concentrations were measured with reversed phase high-performance liquid chromatography (HPLC) and concentration–time data were analyzed by using a non-compartmental approach.

Results

The results of this study suggested a significant genotypic as well as allelic association with valproic acid toxicity for UGT2B7 polymorphic enzymes. The elimination half-life (t1/2=42.2 h) of valproic acid was longer and the clearance rate (CL=947 ml/h) was lower in the poor metabolizers group of UGT2B7 polymorphism who showed toxicity than in the intermediate metabolizers group (t1/2 = 36.5 h, CL = 1,042 ml/h) or the extensive metabolizers group (t1/2 = 27. h, CL = 1,602 ml/h).

Conclusions

Our findings suggest that the UGT2B7 genetic polymorphism plays a significant role in the steady state concentration of valproic acid, and it thereby has an impact on the toxicity of the valproic acid used in the patients with epilepsy.

Authors’ Affiliations

(1)
Department of Pharmaceutics, College of Pharmacy, King Khalid, University
(2)
Department of Pharmacology, College of Pharmacy, King Khalid University
(3)
Faculty of Neuro Surgery, King Khalid University
(4)
Neurosciences Centre, All India Institute of Medical Sciences

References

  1. Chu XM, Zhang LF, Wang GJ, Zhang SN, Zhou JH, Hao HP: Influence of UDP- glucuronosyltransferase polymorphisms on valproic acid pharmacokinetics in Chinese epilepsy patients. Eur J Clin Pharmacol. 2012, 68 (10): 1395-401.View ArticlePubMedGoogle Scholar

Copyright

© Munisamy et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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