GARLIC METABOLISM AND CYTOCHROME P450 MODULATION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There is growing concern over the quality, efficacy and safety of the many herbal products sold over the counter. A major safety concern is the potential for adverse interactions between herbs and drugs. Garlic supplement is among the top selling herbal products in the U.S. The overall objective of this proposed research is to investigate the modulating effects of three commonly used garlic supplements, i.e., Nature Way Garlicin tablet, KAL 1500 garlic oil capsule, and Kyolic Formula 100 Aged Garlic Extract tablets, on the activity of major drug-metabolizing cytochrome P450 enzymes (CYP1A2, 2B6, 2E1, 2C9, 2C19, 2D6, 3A4/5) and the intestinal efflux transporter P-glycoprotein (Pgp) in healthy subjects. In vivo activity of CYPs and Pgp will be measured using "cocktails" of CYP- and Pgp-specific drug substrate probes (caffeine, bupropion, chlorzoxazone, tolbutamide, omeprazole, metoprolol midazolam and digoxin) following acute (2-4 days), chronic (28-39 days), and shortly after following discontinuation (10 days) of treatment with each garlic preparation. Pharmacokinetics of metabolites derived from the bioactive constituents for each of the garlic supplements will also be investigated. Information generated from these probe studies will allow us to predict potential interactions between garlic supplements and prescription drugs.