Impact of cytochrome P-450 inhibition by cimetidine and induction by carbamazepine on the kinetics of hypericin and pseudohypericin in healthy volunteers.
This study evaluated the influence of cimetidine and carbamazepine on the pharmacokinetics of the St. John's wort (SJW) ingredients hypericin and pseudohypericin. In a placebo-controlled, double blind study, 33 healthy volunteers were randomized into three treatment groups that received SJW extract (LI160) with different comedications (placebo, cimetidine, and carbamazepine) for 7 days after a run-in period of 11 days with SJW alone. Hypericin and pseudohypericin pharmacokinetics were measured on days 10 and 17. Between-group comparisons showed no statistically significant differences in AUC(0-24), C(max), and t(max) values for hypericin and pseudohypericin. Within-group comparisons, however, revealed a statistically significant increase in hypericin AUC(0-24) from a median of 119 (range 82-163 microg h/l) to 149 microg h/l (61-202 microg h/l) with cimetidine comedication and a decrease in pseudohypericin AUC(0-24) from a median of 51.0 (16.4-102.9 microg h/l) to 36.4 microg h/l (14.0-102.0 microg h/l) with carbamazepine comedication compared to the baseline pharmacokinetics in each group. Hypericin and pseudohypericin pharmacokinetics were only marginally influenced by comedication with the enzyme inhibitors and inducers cimetidine and carbamazepine.
Johne
Andreas
A
Institute of Clinical Pharmacology, University Medical Center Charité, Humboldt University of Berlin, Campus charité Mitte, Schumannstr. 20/21, 10098, Berlin, Germany. andreas.johne@charite.de
Perloff
Elke S
ES
Bauer
Steffen
S
Schmider
Jürgen
J
Mai
Ingrid
I
Brockmöller
Jürgen
J
Roots
Ivar
I
D000328:Adult; D000873:Anthracenes; D000928:Antidepressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002220:Carbamazepine / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D002927:Cimetidine / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004311:Double-Blind Method; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D020902:Hypericum; D010569:Perylene / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors
D000873:Anthracenes; D000928:Antidepressive Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D002220:Carbamazepine; D010569:Perylene; C004965:hypericin; D002927:Cimetidine; D003577:Cytochrome P-450 Enzyme System; C056602:pseudohypericin