Abstract
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 AUC0-24, Cmax, and tmax values for hypericin and pseudohypericin. Within-group comparisons, however, revealed a statistically significant increase in hypericin AUC0-24 from a median of 119 (range 82–163 μg h/l) to 149 μg h/l (61–202 μg h/l) with cimetidine comedication and a decrease in pseudohypericin AUC0-24 from a median of 51.0 (16.4–102.9 μg h/l) to 36.4 μg h/l (14.0–102.0 μg 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.
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Acknowledgements
This study was supported by Lichtwer Pharma AG (Berlin, Germany). The authors would like to thank Ms. G. Wronski for the preparation of the study medication.
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Johne, A., Perloff, E.S., Bauer, S. et al. Impact of cytochrome P-450 inhibition by cimetidine and induction by carbamazepine on the kinetics of hypericin and pseudohypericin in healthy volunteers. Eur J Clin Pharmacol 60, 617–622 (2004). https://doi.org/10.1007/s00228-004-0823-3
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DOI: https://doi.org/10.1007/s00228-004-0823-3