Abstract
Widespread use of any (herbal) medical product calls for the investigation of possible interactions with other medicines. While pharmacovigilance allows the continuous monitoring of potential signals, the increasing simultaneous use of diverse medications makes this monitoring difficult to interpret and, of course, does not explain possible mechanism of actions of such interactions. Many of these interactions occur via induction or inhibition of the CYP P450 enzyme system, a superfamily of membrane-bound, heme-thiolate proteins, which are principally responsible for phase 1 oxidative metabolism and detoxification of xenobiotics and endobiotics. The German regulatory authority, for example, requires in vitro assessment of herbal medicinal products on the main cytochrome P450 enzymes involved in drug metabolism [1]. In a fluorometric supersome assay, products containing Echinacea ethanol water extracts were evaluated. These extracts vary widely in their inhibitory activity on CYP3A4 (IC50 values: 12.71µg/ml -1812µg/ml) [2]. Therefore, conclusions drawn using one specific extract cannot necessarily be generalized to others, similarly extracted ones derived from the same botanical drug. Individual alkylamides showed moderate inhibitory activity against CYP enzymes, but these effects are – at the doses of Echinaforce® normally used – unlikely to be of clinical concern. Other constituents contribute to the extract's observed in vitro effects and are currently under investigation [3]. These data provide a sound basis for assessing the interaction potential of Echinacea preparations studied. While additional studies on other potential targets may be desirable, overall, the data contribute important information to the safety profile of this drug and indicate that these preparations are likely to be safe if used under a normal therapeutic regimen.
Funding: Our studies on herbal medicines and the cytochrome system are partially sponsored by Bioforce, CH and by the European Union (FP6).
References:
[1] BfArM (2004) http://www.bfarm.de/cln_042/nn_424630/DE/Arzneimittel/besTherap/amPflanz/ampflanz-node.html (Last accessed 20.08.2006). [2] Modarai, M. et al. (2007) J. Pharm. Pharmacol. 59: 567–573. [3] Modarai, M., et al. (2007) GA congress, poster abstract