Adverse events due to drug-drug and/or herb-drug interactions are of serious concern and a
major cause of morbidity and mortality. Resveratrol is a polyphenol antioxidant that has been
identified in over 70 species and is suggested to be the constituent in red wine responsible
for cardioprotective effects. The potential health benefits of resveratrol supplements are
highly extolled in the alternative medicine industry and daily doses are up to 5 grams are
being studied. While there are potential health benefits of high doses of resveratrol, for
patients taking other drugs metabolized by CYP3A4, such as transplant medications,
chemotherapies and HMG-CoA reductase inhibitors, there may be a clinically significant
herb-drug interaction.
We, the investigators, have shown in vitro that resveratrol is a mechanism-based inhibitor of
cytochrome P450 3A4 (CYP3A4). Based on our in vitro evidence and literature reports of the
pharmacokinetics of resveratrol, we hypothesize that resveratrol will be a potent in vivo
mechanism-based inhibitor of intestinal CYP3A4 enzymes. To date, there are no clinical
studies that address the potential for a resveratrol-drug interaction. We propose to test
whether single and multiple doses of resveratrol alter the pharmacokinetics of midazolam, a
prototypic CYP3A4 probe drug.