Document Detail


Differential effects of Saint John's Wort (hypericum perforatum) on the urinary excretion of D-glucaric acid and 6beta-hydroxycortisol in healthy volunteers.
MedLine Citation:
PMID:  12483450     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Steffen Bauer; Elke Störmer; Reinhold Kerb; Andreas Johne; Jürgen Brockmöller; Ivar Roots
Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article     Date:  2002-11-12
Journal Detail:
Title:  European journal of clinical pharmacology     Volume:  58     ISSN:  0031-6970     ISO Abbreviation:  Eur. J. Clin. Pharmacol.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-12-16     Completed Date:  2003-05-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1256165     Medline TA:  Eur J Clin Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  581-5     Citation Subset:  IM    
Affiliation:
Institute of Clinical Pharmacology, University Medical Centre Charité, Humboldt University of Berlin, Schumannstrasse 20/21, 10098 Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
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:
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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