Pharmacokinetic Drug Interactions between Anticancer Therapeutics and Drugs of Complementary Medicine: Mechanisms and Clinical Relevance

Pharmacokinetic Drug Interactions between Anticancer Therapeutics and Drugs of Complementary Medicine: Mechanisms and Clinical Relevance Herbal preparations are an important part of complementary medicine and enjoy great popularity among cancer patients due to their broad therapeutical window and low rate of adverse effects. For example, extracts from St. John's wort reduce depression without the typical side effects of synthetic antidepressant drugs. According to this, herbal preparations are able to improve the quality of life or, as in the case of mistletoe (Viscum album) and Indian olibanum (Boswellia serrata), exhibit an additional therapeutic effect. However, herbal extracts are complex mixtures which, comparable to synthetic drugs, can change the bioavailability of drugs and therefore deteriorate the benefit-risk ratio of chemotherapeutics at which an increased toxicity or reduced therapeutic value is caused by an inhibition or induction of drug metabolism and/or transport. St. John's wort extracts containing hyperforin, for instance, cause a clinically relevant reduction of the bioavailability of the anticancer drugs irinotecan and imatinib by 41 and 30%, respectively, because hyperforin increases the expression of the cytochrome P450 enzyme 3A4 (CYP3A4) and the efflux transporter P-glycoprotein (P-gp), which are primarily responsible for the metabolism and transport of anticancer drugs. However, a clinically relevant inhibition of CYP3A4 or P-gp by herbal extracts has so far not been shown for anticancer therapeutics. However, this appears to be very likely, since for goldenseal (Hydrastis canadensis) and Wu Wei Zi (Schisandra sphenanthera/chinensis), which are readily available via the internet, in vitro and in vivo studies have shown a significant inhibition of CYP3A4 and P-gp.