Effect of glycyrrhizin on CYP2C19 and CYP3A4 activity in healthy volunteers with different CYP2C19 genotypes

Abstract

1. The objective of this study was to investigate the interaction between glycyrrhizin and omeprazole and observe the effects of glycyrrhizin on CYP2C19 and CYP3A4 activities in healthy Chinese male volunteers with different CYP2C19 genotypes.

2. Eighteen healthy subjects (six CYP2C19*1/*1, five CYP2C19*1/*2, one CYP2C19*1/*3, five CYP2C19*2/*2 and one CYP2C19*2/*3) were enrolled in a two-phase randomized crossover trial. In each phase, all subjects received placebo or glycyrrhizin salt tablet 150 mg twice daily for 14 consecutive days. The pharmacokinetics of omeprazole (20 mg orally on day 15) was determined for up to 12 h following administration by high-performance liquid chromatography.

3. After 14-day treatment of glycyrrhizin, plasma omeprazole significantly decreased, and those of omeprazole sulfone significantly increased. However, plasma concenetrations of 5-hydroxyomeprazole did not significantly change. The ratio of AUC_0–∞ of omeprazole to omeprazole sulfone decreased by 43.93% ± 13.56% (p = 0.009) in CYP2C19*1/*1, 44.85% ± 14.84% (p = 0.002) in CYP2C19*1/*2 or *3 and 36.16% ± 7.52% (p < 0.001) in CYP2C19*2/*2 or *3 while those of omeprazole to 5-hydroxyomeprazole did not change significantly in all three genotypes. No significant differences in glycyrrhizin response were found among CYP2C19 genotypes.

4. Glycyrrhizin induces CYP3A4-catalyzed sulfoxidation of omeprazole and leads to decreased omeprazole plasma concentrations, but has no significant impact on CYP2C19-dependent hydroxylation of omeprazole.

Keywords::

• Glycyrrhizin
• induction
• CYP3A4
• omeprazole
• pharmacokinetics

Acknowledgements

This work was supported by research grants from the National Natural Science Foundation of China 30472054, 430528026, 30300428, 30672497, 30500623, and 30572226, and by the China Medical Board of New York grants 01-755.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.