Acta pharmacologica Sinica, 2007-10, Vol.28 (10), p.1685-1692
2007
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- Autor(en) / Beteiligte
- Titel
- Herbal medicine Yin Zhi Huang induces CYP3A4-mediated sulfoxidation and CYP2C19-dependent hydroxylation of omeprazole
- Ist Teil von
- Acta pharmacologica Sinica, 2007-10, Vol.28 (10), p.1685-1692
- Ort / Verlag
- United States: Nature Publishing Group
- Erscheinungsjahr
- 2007
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Aim： To explore the potential interactions between Y/n 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 CYP2C 19＊ 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1671-4083eISSN: 1745-7254DOI: 10.1111/j.1745-7254.2007.00617.xTitel-ID: cdi_proquest_journals_213015632
- Format
- –
- Schlagworte
- 2-Pyridinylmethylsulfinylbenzimidazoles - blood, Adult, Anti-Ulcer Agents - blood, Anti-Ulcer Agents - metabolism, Anti-Ulcer Agents - pharmacokinetics, Area Under Curve, Artemisia - chemistry, Aryl Hydrocarbon Hydroxylases - genetics, Aryl Hydrocarbon Hydroxylases - metabolism, Cross-Over Studies, CYP2C19, CYP3A4, Cytochrome P-450 CYP2C19, Cytochrome P-450 CYP3A - genetics, Cytochrome P-450 CYP3A - metabolism, Drug Combinations, Drugs, Chinese Herbal - isolation & purification, Drugs, Chinese Herbal - pharmacology, Genotype, Herb-Drug Interactions, Humans, Hydroxylation - drug effects, Male, Omeprazole - analogs & derivatives, Omeprazole - blood, Omeprazole - metabolism, Omeprazole - pharmacokinetics, Plants, Medicinal - chemistry, Safrole - analogs & derivatives, Safrole - metabolism, 中草药