Echinacea metabolism and drug interactions: The case for standardization of a complementary medicine

The herbal medicine, Echinacea, is used for treatment and prevention of upper respiratory tract infections. Among the phytochemicals found in Echinacea, the bioavailable alkylamides are thought to be the compounds responsible for its effects on the human immune system. Cytochrome P450 enzymes (P450s) appear to be the principal system responsible for the metabolism of Echinacea components and most of the main hepatic and some extrahepatic isoforms appear to be involved. Epoxide formation, N-dealkylation and hydroxylation are the main metabolic pathways mediated by P450s. Interactions with P450s determine the circulating concentrations and duration of action of these phytochemicals as well as any potential interactions with other chemicals. Most research to date has focused on the potential of Echinacea to interact with other drugs. Literature reports are equivocal and comparisons between studies are difficult as the phytochemical composition of the preparations examined is rarely assessed. Certain alkylamides containing a terminal acetylene appear to exert a time- and NADPH-dependent inhibition on the metabolism of other compounds. However as there are no industry standardization requirements, differences in the relative concentrations of individual alkylamides between preparations could alter the potential for interactions. A thorough phytochemical analysis of samples investigated is necessary in further studies so that sound conclusions can be drawn regarding the potential for inter-individual variation in pharmacokinetics and therapeutic effects and interactions with other chemicals. Moreover standardization of alkylamide content may allow the exploitation of beneficial interactions between alkylamide components to enhance the therapeutic effect of this widely used complementary medicine.