title: Differential effects of Saint John's Wort (hypericum perforatum) on the urinary excretion of D-glucaric acid and 6beta-hydroxycortisol in healthy volunteers.
abstract: 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.affiliation: Institute of Clinical Pharmacology, University Medical Centre Charité, Humboldt University of Berlin, Schumannstrasse 20/21, 10098 Berlin, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Bauer
authors.forename: Elke
authors.initials: E
authors.lastname: Störmer
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kerb
authors.forename: Andreas
authors.initials: A
authors.lastname: Johne
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brockmöller
authors.forename: Ivar
authors.initials: I
authors.lastname: Roots
mesh_terms: D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D051544:Cytochrome P-450 CYP3A; D004790:Enzyme Induction; D005260:Female; D005937:Glucaric Acid / Q000652:urine*; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine*; D020902:Hypericum / Q000737:chemistry*; D008297:Male; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis; D010936:Plant Extracts / Q000494:pharmacology
chemical_list: D010936:Plant Extracts; C001380:6 beta-hydroxycortisol; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D005937:Glucaric Acid; D006854:Hydrocortisone