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UDP-glucuronosyl transferases (UGT) mediate a conjugation reaction by glucuronidation of various clinically important drugs. The functional significance of genetic polymorphisms in these UGTs are main concern of the current researchers of UGTs. Valproate (valproic acid) is an antiepileptic drug glucuronidated mainly by UGT2B7. We investigated the effect of genetic polymorphism on pharmacokinetics of valproate in healthy normal volunteers. Before the clinical study, we screened genotype of UGT2B7-T801A (T:*1, A:*2). Twenty three healthy subjects were enrolled and grouped with regard to the UGT2B7 genotype. The pharmacokinetic profile of valproate was characterized after valproate administration (600 mg once daily for 5 days). The plasma concentrations of valproate were analyzed before and 1, 1.25, 1.5, 2, 2.5, 3, 5, 7, 9, 13, 25, 49 hours after 5 th valproate administration by TDX with FPIA method. Although the pharmacokinetic profiles of valproate did not showed significant differences between the UGT2B7 genotype groups, a trend of decrease of clearance as increase of UGT2B7*2 allele was observed. Oral clearance of valproate in the UGT2B7*2/*2 group was 66% of that of the UGT2B7*1/*1 group. The results suggest that the UGT2B7*2/*2 genotype group possibly has a decreased clearance of valproate. Further study may be required to clarify the results.

Effect of UGT2B7 Genotype on Pharmacokinetics of Valproate in Human Healthy Subjects