Phytochemical Modulators of Human Drug Metabolism: An Introduction to Herb-Drug Interactions

Over the past decade, an upsurge in botanical supplement usage, particularly within the United States, has engendered concerns among health care professionals regarding herb-drug interactions. Such concerns may be well founded given that recent surveys indicate 21 – 31% of prescription drug users take medications concomitantly with herbal dietary supplements, oftentimes without notifying their physician. Two general categories of herb-drug interactions have been recognized: pharmacodynamic and pharmacokinetic. Pharmacodynamic herb-drug interactions are those in which a botanical supplement can either enhance or diminish a drug's pharmacological activity without affecting its metabolism or transport. On the other hand, pharmacokinetic herb-drug interactions involve phytochemical-mediated alterations in a drug's metabolism and/or transport. One mechanism that appears to underlie many herb-drug interactions is the modulation of human cytochrome P450 drug metabolizing enzyme (CYP450) activity. CYP450 s are heme-containing monooxygenases located in the small intestine, liver, and other tissues that play pivotal roles in the detoxification and bioactivation of diverse xenobiotic substances. Phytochemical-mediated changes in the activity of specific CYP450 isoforms (e.g. CYP1A2, CYP2D6, CYP3A4, etc.) may significantly alter the efficacy or toxicity of conventional medications whose biotransformation pathways are dependent on these same isoforms. Modulation of drug transport protein activity (e.g. P-glycoprotein, organic anion transporting polypeptide, breast cancer resistance protein, etc.) is another mechanism by which phytochemicals can affect the pharmacokinetic profile of conventional medications. The purpose of this presentation is to provide an introduction to herb-drug interactions using clinically relevant examples of each category.