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 ext...

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Bibliographic Details
Published in:European journal of clinical pharmacology 2004-11, Vol.60 (9), p.617-622
Main Authors: JOHNE, Andreas, PERLOFF, Elke S, BAUER, Steffen, SCHMIDER, Jürgen, MAI, Lngrid, BROCKMÖLLER, Jürgen, ROOTS, Ivar
Format: Article
Language:English
Subjects:
Adult
Antidepressive Agents - blood
Antidepressive Agents - pharmacokinetics
Area Under Curve
Biological and medical sciences
Carbamazepine - pharmacology
Chromatography, High Pressure Liquid
Cimetidine - pharmacology
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System - biosynthesis
Double-Blind Method
Drug Interactions
Enzyme Inhibitors - pharmacology
Humans
Hypericum
Medical sciences
Perylene - analogs & derivatives
Perylene - blood
Perylene - pharmacokinetics
Pharmacology. Drug treatments
Time Factors
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Summary: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.
ISSN:0031-6970
1432-1041
DOI:10.1007/s00228-004-0823-3