Differential effects of Saint John's Wort (hypericum perforatum) on the urinary excretion of D-glucaric acid and 6beta-hydroxycortisol in healthy volunteers.
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.
Bauer
Steffen
S
Institute of Clinical Pharmacology, University Medical Centre Charité, Humboldt University of Berlin, Schumannstrasse 20/21, 10098 Berlin, Germany.
Störmer
Elke
E
Kerb
Reinhold
R
Johne
Andreas
A
Brockmöller
Jürgen
J
Roots
Ivar
I
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
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