| Differential effects of Saint John's Wort (hypericum perforatum) on the urinary excretion of D-glucaric acid and 6beta-hydroxycortisol in healthy volunteers. | |
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MedLine Citation:
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PMID: 12483450 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: We investigated the effects of treatment with Saint John's wort (hypericum perforatum) extract on the urinary excretion of D-glucaric acid, 6beta-hydroxycortisol, and free cortisol in order to assess the effect of this extract on the activity of hepatic xenobiotic metabolizing enzymes. METHODS: Forty-eight healthy volunteers (25 male and 23 female) received a daily dose of 1800 mg hypericum extract for 14 days. Urinary excretion of D-glucaric acid, 6beta-hydroxycortisol, and free cortisol was measured in 24-h urine samples on the day preceding the initiation of hypericum treatment and after 14 days of treatment. D-Glucaric acid was measured enzymatically. Cortisol and 6beta-hydroxycortisol were quantified using high-performance liquid chromatography with ultraviolet detection. RESULTS: Urinary excretion of D-glucaric acid was unaffected after a 14-day treatment with Saint John's wort extract (26.7 micromol/day vs 27.7 micromol/day; 95% confidence interval of the difference: -1.9 to 3.8). The urinary excretion of 6beta-hydroxycortisol increased from a mean baseline value of 254 microg/day to 369 microg/day (P<0.0001) indicating induction of CYP3A. While the excretion of free cortisol was unaltered, the ratio of 6beta-hydroxycortisol to free cortisol changed significantly from 9.9 at baseline to 14.3 (95% confidence interval of the difference: 2.3-6.5) after Saint John's wort treatment. CONCLUSIONS: High-dose treatment with Saint John's wort extract induced CYP3A activity in healthy volunteers as evidenced by increased 6beta-hydroxycortisol excretion. This enzyme induction most likely contributes to the decreased bioavailability observed upon co-administration of various drugs with Saint John's wort extract. The D-glucuronic acid pathway appeared unaffected by Saint John's wort. |
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Authors:
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Steffen Bauer; Elke Störmer; Reinhold Kerb; Andreas Johne; Jürgen Brockmöller; Ivar Roots |
Publication Detail:
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Type: Clinical Trial; Comparative Study; Journal Article Date: 2002-11-12 |
Journal Detail:
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Title: European journal of clinical pharmacology Volume: 58 ISSN: 0031-6970 ISO Abbreviation: Eur. J. Clin. Pharmacol. Publication Date: 2002 Dec |
Date Detail:
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Created Date: 2002-12-16 Completed Date: 2003-05-12 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1256165 Medline TA: Eur J Clin Pharmacol Country: Germany |
Other Details:
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Languages: eng Pagination: 581-5 Citation Subset: IM |
Affiliation:
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Institute of Clinical Pharmacology, University Medical Centre Charité, Humboldt University of Berlin, Schumannstrasse 20/21, 10098 Berlin, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aryl Hydrocarbon Hydroxylases / biosynthesis Cytochrome P-450 CYP3A Enzyme Induction Female Glucaric Acid / urine* Humans Hydrocortisone / analogs & derivatives*, urine* Hypericum / chemistry* Male Oxidoreductases, N-Demethylating / biosynthesis Plant Extracts / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Plant Extracts; 25525-21-7/Glucaric Acid; 50-23-7/Hydrocortisone; 53-35-0/6 beta-hydroxycortisol; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/Cytochrome P-450 CYP3A; EC 1.5.-/Oxidoreductases, N-Demethylating |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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