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期刊论文
St John’s wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole
CLINICAL PHARMACOLOGY & THERAPEUTICS 2004; 75 (3): 191-7,-0001,():
Objective: St John's wort, an extract of the medicinal plant Hypericum perforatum, is widely used as an herbal antidepressant. Although the ability of St John's wort to induce cytochrome P450 (CYP) 3A4-mediated reaction has been well established, the effect on CYP2C19 is still not determined. Thus the objective of this study was to determine the impact of St John's wort on the pharmacokinetic profiles of omeprazole and its metabolites. Methods: Twelve healthy adult men (6 CYP2C19*1/CYP2C19*1, 4 CYP2C19*2/CYP2C19*2 and 2 CYP2C19*2/CYP2C19*3) were nrolled in a 2-phase randomized crossover design. In each phase the volunteers received placebo or a 300-mg St John's wort tablet 3 times daily for 14 days. Then all subjects took a 20-mg omeprazole capsule orally. Blood samples were collected up to 12 hours after omeprazole administration. Omeprazole and its metabolites were quantified by use of HPLC with ultraviolet detection. Results: Omeprazole and its metabolites all exhibit CYP2C19 genotype-dependent pharmacokinetic profiles. After a 14-day treatment with St John's wort, substantial decreases in plasma concentrations of omeprazole were observed. The peak plasma concentration (Cmax) significantly decreased by 37.5%±13.3% (P=.001) in CYP2C19*2/CYP2C19*2 or *3 and by 49.6%±20.7% (P=.017) in CYP2C19*1/CYP2C19*1; the area under the concentration-time curve extrapolated to infinity [AUC(0-∞)] decreased by 37.9%±21.3% (P=.014) and 43.9%±23.7% (P=.011) in CYP2C19 mutant and wild genotypes, respectively. Moreover, the Cmax and AUC(0-∞) of omeprazole sulfone increased by 160.3%±45.5% (P=.001) and by 136.6%±84.6% (P=.014), 155.5%±58.8% (P=.001), and 158.7%±101.4% (P=.017) in mutant and wild genotypes, respectively. St John's wort increased the Cmax of 5-hydroxyomeprazole by 38.1% 30.5% (P=.028) and the AUC(0-∞) by 37.2%±26% (P=.005) in CYP2C19 wild-type subjects, whereas it did not produce any significant alterations to the corresponding pharmacokinetic parameters in subjects with variant genotypes. Conclusion: St John's wort induces both CYP3A4-catalyzed sulfoxidation and CYP2C19-dependent hydroxylation of omeprazole and enormously decreases the plasma concentrations of omeprazole. Clinically relevant interactions with other drugs may occur and must be taken into account when St John's wort is being taken.
【免责声明】以下全部内容由[周宏灏]上传于[2005年01月19日 21时16分45秒],版权归原创者所有。本文仅代表作者本人观点,与本网站无关。本网站对文中陈述、观点判断保持中立,不对所包含内容的准确性、可靠性或完整性提供任何明示或暗示的保证。请读者仅作参考,并请自行承担全部责任。
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