The influence of UGT2B7 genotype on valproic acid pharmacokinetics in Chinese epilepsy patients

Abstract

The aim of this study was to investigate the distribution and frequency of genetic polymorphisms in uridine diphosphate glucuronosyltransferase-2B7 (UGT2B7) in epilepsy patients and to evaluate the effect of these on the metabolism of valproic acid (VPA). Single nucleotide polymorphisms in UGT2B7 were investigated in 102 epilepsy patients using DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism analysis. The steady-state plasma concentrations of VPA were determined in these patients, who had received VPA (approx. 500-1000 mg/day) for at least 2 weeks. Fourteen patients had the CC genotype at UGT2B7 C802T, 46 carried CT, and 42 carried the TT genotype. At UGT2B7 G211T, 78 patients had the GG genotype, 23 carried GT, and one individual had the TT genotype. The standardized trough plasma concentration of VPA was much lower in those patients with a T allele at UGT2B7 C802T than in those with the CC genotype (TT, 2.11 ± 1.26; CT, 2.31 ± 1.25; CC, 3.02 ± 1.32 μg kg mL(-1) mg(-1), p < 0.01). However, UGT2B7 G211T polymorphisms had no influence on the plasma concentration of VPA (GG, 2.28 ± 1.32, GT, 2.303 ± 1.38 μg kg mL(-1) mg(-1)). These results suggested that UGT2B7 C802T may be an important determinant of individual variability in the pharmacokinetics of VPA and that it may be necessary to increase the VPA dose for individuals with a T allele in order to achieve the therapeutic range of 50-100 μg/mL.