Life-styleA randomized, double-blind, dose-ranging, pilot trial of piperine with resveratrol on the effects on serum levels of resveratrolBailey, Howard H.a; Johnson, Jeremy J.b,,c; Lozar, Tajad; Scarlett, Cameron O.b; Wollmer, Barbara W.a; Kim, KyungManna,,e; Havinghurst, Thomase; Ahmad, NihalfAuthor Information aUniversity of Wisconsin, Carbone Cancer Center bAnalytical Instrumentation Center, University of Wisconsin, School of Pharmacy, Madison, Wisconsin cDepartment of Pharmacy Practice, University of Illinois Cancer Center, University of Illinois, Chicago, Illinois dFaculty of Medicine, University of Ljubljana, Ljubljana, Slovenia eDepartment of Biostatistics and Medical Informatics fDepartment of Dermatology, University of Wisconsin, Madison, Wisconsin, USA Received 28 April 2020 Accepted 25 June 2020 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.eurjcancerprev.com). Correspondence to Howard H. Bailey, MD, University of Wisconsin Carbone Cancer Center, Box 6164 Clinical Science Center-K4/610, 600 Highland Ave, Madison, WI 53792, USA, Tel: +608 263 8624; fax: +608 263 8613; e-mail: [email protected] European Journal of Cancer Prevention: May 2021 - Volume 30 - Issue 3 - p 285-290 doi: 10.1097/CEJ.0000000000000621 Buy SDC Metrics Abstract Resveratrol (3,4,5-trihydroxystilbene) is a naturally occurring phytoalexin with purported health-promoting effects, but with limited oral bioavailability. Our prior murine modeling research observed enhanced resveratrol bioavailability with piperine co-administration. In this study, single-dose pharmacokinetics of resveratrol with or without piperine and the associated toxicities were studied on a cohort of healthy volunteers. We performed a double-blind, randomized, three-arm pilot study. Participants were randomized to receive a single dose of resveratrol 2.5 g, with piperine in 0 mg, 5 mg, or 25 mg dose. An improved liquid chromatography/mass spectrometry assay was used to determine serum levels of resveratrol and resveratrol-glucuronide. Baseline through 24 h post-study drug serum analyses were performed and adverse events were followed for 30 days. Twenty-four participants were enroled. No significant relationship between dose and pharmacokinetic values were found. In the sex stratified analysis, Cmax for resveratrol in women showed a trend (P = 0.057) toward an increase with piperine. Pharmacokinetic values for resveratrol were: Cmax – 18.5 ± 16 ng/mL resveratrol alone, 29 ± 29 resveratrol + 5 mg piperine, 16 ± 13 resveratrol + 25 mg piperine; area under the concentration × time curve – 1270 ± 852 ng/h/mL resveratrol alone, 2083 ± 2284 resveratrol + 5 mg piperine, 1132 ± 222 resveratrol + 25 mg piperine. All subjects tolerated their protocol therapy with minimal to no toxicity and no evidence of differences between the three groups. The co-administration of resveratrol with piperine at 5 and 25 mg doses did not sufficiently alter the pharmacokinetics of resveratrol or resveratrol-glucuronide to demonstrate the significant enhancement observed in murine modeling. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.