| Popis: |
Plant secondary metabolites (PSMs) have been components of man's diet for millennia and are believed to have played a significant role in steering the functional development of xenobiotic metabolizing enzymes (XMEs) and transporters within the human gastrointestinal tract. Only recently, however, PSMs have been recognized as modulators of human drug disposition. Despite exposure to thousands of structurally diverse dietary phytochemicals, only a few appear to significantly modulate human drug-metabolizing enzymes and transporters. In some instances, these interactions may have beneficial effects, such as cancer prevention (i.e., isothiocyanates in cruciferous vegetables), whereas others may dramatically affect the pharmacokinetics of concomitantly administered drugs (i.e., furanocoumarins in grapefruit juice). In today's global economy, the opportunity for exposure to more exotic phytochemicals is significantly enhanced. Formulated as concentrated phytochemical extracts, botanical dietary supplements are vehicles for a host of PSMs rarely encountered in the normal diet. When taken with conventional medications, botanical dietary supplements may give rise to clinically significant herb–drug interactions. These interactions stem from phytochemical-mediated induction and/or inhibition of human drug-metabolizing enzymes and transporters. In this chapter, the herb–drug interaction risks and mechanisms for several of the most popular dietary supplements are discussed. Botanicals most likely to produce clinically important herb–drug interactions are those whose phytochemicals act as mechanism-based inhibitors of cytochrome P450 enzyme (CYP) activity (e.g., Hydrastis canadensis, Piper nigrum, and Schisandra chinensis) or function as ligands for orphan nuclear receptors (e.g., Hypericum perforatum). In addition, several external factors unrelated to phytochemical pharmacology can augment the drug interaction potential of botanical supplements. Keywords: Botanical dietary supplements; citrus juices; cruciferous vegetables; cytochrome P450 enzymes; black cohosh; black pepper; Echinacea; garlic; Ginkgo biloba; ginseng; goldenseal; herb-drug interactions; kava; milk thistle; phytochemicals; piperine; Schisandra; St. John's wort |
