Impact of cytochrome P-450 inhibition by cimetidine and induction by carbamazepine on the kinetics of hypericin and pseudohypericin in healthy volunteers.

Author(s): Johne A, Perloff ES, Bauer S, Schmider J, Mai I, Brockmoller J, Roots I

Affiliation(s): Institute of Clinical Pharmacology, University Medical Center Charite, Humboldt University of Berlin, Campus charite Mitte, Schumannstr. 20/21, 10098, Berlin, Germany. andreas.johne@charite.de

Publication date & source: 2004-11, Eur J Clin Pharmacol., 60(9):617-22. Epub 2004 Sep 15.

Publication type: Clinical Trial; Randomized Controlled Trial

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.