Resveratrol and Midazolam Metabolism
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|ClinicalTrials.gov Identifier: NCT01173640|
Recruitment Status : Completed
First Posted : August 2, 2010
Last Update Posted : October 31, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Healthy||Drug: Midazolam Dietary Supplement: resveratrol (single dose) Dietary Supplement: resveratrol (multiple dose)||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Resveratrol and Midazolam Metabolism|
|Study Start Date :||July 2010|
|Actual Primary Completion Date :||February 2011|
|Actual Study Completion Date :||February 2011|
Experimental: Midazolam Alone
Baseline pharmacokinetics. On Study Visit Day 1, subjects will receive a single oral dose of midazolam (2 mg). Blood and urine will be collected to measure midazolam and its metabolites, and resveratrol and its metabolites.
2 mg oral dose
Other Name: Versed
Experimental: Single dose resveratrol
On Study Visit Day 8, subjects will receive a 1 g oral dose of resveratrol followed 2 hours later by a single oral dose of midazolam (2 mg). Blood and urine will be collected to measure midazolam and its metabolites, and resveratrol and its metabolites.
2 mg oral dose
Other Name: VersedDietary Supplement: resveratrol (single dose)
1 g oral dose
Experimental: Multiple dose resveratrol
Between Study Visit Days 8 and 15, subjects will take a 1 g dose of resveratrol daily. On Study Visit Day 15, subjects will receive a 1 g oral dose of resveratrol followed 2 hours later by a single oral dose of midazolam (2 mg). Blood and urine will be collected to measure midazolam and its metabolites, and resveratrol and its metabolites.
2 mg oral dose
Other Name: VersedDietary Supplement: resveratrol (multiple dose)
1 g oral dose for 8 days
- Inhibition of midazolam clearance [ Time Frame: 3 study visit days ]The primary aim will be to determine if resveratrol causes inhibition of intestinal and hepatic CYP3A4 enzymes as determined by oral midazolam clearance following single and multiple doses of resveratrol, respectively.
- Resveratrol accumulation [ Time Frame: 3 study visit days ]Secondary aims will be to measure circulating levels of resveratrol and its conjugated metabolites following single and multiple doses of resveratrol and to determine resveratrol accumulation in low density lipoproteins (LDL).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01173640
|United States, Washington|
|University of Washington|
|Seattle, Washington, United States, 98195|
|Principal Investigator:||Yvonne S Lin, PhD||University of Washington|
|Principal Investigator:||Ryan Bradley, ND, MPH||Bastyr University|
|Principal Investigator:||Kelsey Hanson, MS||University of Washington|