Herbal medicine Yin Zhi Huang induces CYP3A4-mediated sulfoxidation and CYP2C19-dependent hydroxylation of omeprazole

Aim: To explore the potential interactions between Yin Zhi Huang (YZH) and omeprazole, a substrate of CYP3A4 and CYP2C19. Methods: Eighteen healthy volunteers, including 6 CYP2C19*1/*1, 6 CYP2C19*1/*2 or *3 and 6 CYP2C19*2/*2 were enrolled in a 2-phase, randomized, crossover clinical trial. In each phase, the volunteers received either placebo or 10 mL YZH oral liquid, 3 times daily for 14 d. Then all the patients took a 20 mg omeprazole capsule orally. Blood samples were collected up to 12 h after omeprazole administration. Plasma concentrations of omeprazole and its metabolites were quantified by HPLC with UV detection. Results: After 14 d of treatment of YZH, plasma omeprazole significantly decreased and those of omeprazole sulfone and 5-hydroxyomeprazole significantly increased. The ratios of the area under the plasma concentration-time curves from time 0 to infinity (AUC((0-infinity)) of omeprazole to 5-hydroxyomprazole and those of omeprazole to omeprazole sulfone decreased by 64.80%+/- 12.51% (P=0.001) and 63.31%+/- 18.45% (P=0.004) in CYP2C19*1/*1, 57.98%+/- 14.80% (P=0.002) and 54.87%+/- 18.42% (P=0.003) in CYP2C19*1/*2 or *3, and 37.74%+/- 16.07% (P=0.004) and 45.16%+/- 15.54% (P=0.003) in CYP2C19*2/*2, respectively. The decrease of the AUC((0-infinity)) ratio of omeprazole to 5-hydroxyomprazole in CYP2C19*1/*1 and CYP2C19*1/*2 or *3 was greater than those in CYP2C19*2/*2 (P=0.047 and P=0.009). Conclusion: YZH induces both CYP3A4-catalyzed sulfoxidation and CYP2C19-dependent hydroxylation of omeprazole leading to decreases in plasma omeprazole concentrations.