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

Murali, Munisamy and Gauthaman, Karunakaran and Vivekanandhan, Subbiah and Manjari M, Tripathi (2014) Pharmacogenetics of uridine diphosphate glucuronosyltransferase (UGT2B7) genetic polymorphism on valproic acid pharmacokinetics in epilepsy. In: http://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-15-S2-P3.

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Abstract

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.

Item Type: Conference or Workshop Item (Paper)
Subjects: Medicine and Surgery
Pharmaceutical Sciences
Pharmacy
Biology
Divisions: College of Pharmacy > Pharmacy
Depositing User: GAUTHAMAN Karunakaran
Date Deposited: 11 Mar 2017 12:50
Last Modified: 11 Mar 2017 12:50
URI: http://eprints.kku.edu.sa/id/eprint/485

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