Pharmacokinetic Herb-Drug Interactions of Echinacea

Echinacea preparations are one of the best sold herbal over-the-counter remedies. They are commonly used for the treatment of the common cold, bronchitis and inflammation of the mouth and pharynx. Much is known already about pharmacodynamic effects and the pharmacological activity of the main constituents (polysaccharides, glycoproteins, caffeic acid derivatives and alkamides). However, there is only few information available on the influence of drug metabolism by Echinacea. Metabolic herb-drug interactions can result in tremendous variability in pharmacokinetics of synthetic drugs, with changes in concentrations of over 10-fold. In the intended investigations, first the absolute bioavailability shall be determined for the main Echinacea alkamides, the dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides, to provide an indication for the metabolic impact of p-glycoprotein. Further investigations will use phytochemically characterized extracts of Echinacea angustifolia, E. purpurea, E. pallida roots (60 % and 20 % ethanol) and E. purpurea aerial parts (60 % and 20 % ethanol extract, and pressed juice), but also isolated pure alkamides, to systematically evaluate the potential influence of the different Echinacea constituents on the activity of cytochrome P-450 enzymes and p-glycoprotein in in vivo and in vitro pharmacokinetic herb-drug interaction models in order to address the following specific aims: I. To assess the influence of specific Echinacea constituents on the activity of specific cytochrome enzymes (CYP3A4, CYP2D6 and CYP1A2) and p-glycoprotein. II. To evaluate for which Echinacea preparations, species, plant parts and extraction procedures (pressed juice or hydroalcoholic tinctures) drug interaction are most likely. III. To ascertain the optimal dosage regime with a pharmacokinetic/pharmacodynamic (PK/PD)-modelling. The University of Florida, and in particular the Department of Pharmaceutics in Gainesville, is well known for providing a world-class research environment for the performing of pharmacokinetic and herb-drug interaction studies with herbal medicinal products. The studies will improve the safe and rational use of Echinacea preparations.