Abstract
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-∞) 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-∞) 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.
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Project supported by grants from the National Natural Science Foundation of China (No F30130210 and C30200346), China Medical Board (No 99-697 and 01-755), Hunan Health Research Foundation of Traditional Chinese Medicine (No 204041), the Postdoctoral Science Foundation of Central South University and the Cultivation Fund of the Key Scientific and Technical Innovation Project, Ministry of Education of China (No 704036).
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Fan, L., Wang, G., Wang, Ls. et al. Herbal medicine Yin Zhi Huang induces CYP3A4-mediated sulfoxidation and CYP2C19-dependent hydroxylation of omeprazole. Acta Pharmacol Sin 28, 1685–1692 (2007). https://doi.org/10.1111/j.1745-7254.2007.00617.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00617.x
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