Resveratrol exhibits a wide range of biological properties, including anti-glycation, antioxidant, anti-inflammation, neuroprotective (including against advanced dementia and Alzheimer’s disease), anti-cancer, and anti-aging activity in experimental models. Unfortunately, this compound exhibits low bioavailability and solubility, requiring large doses that can cause nausea and GI distress. JOTROLTM is a micellar 10% resveratrol solubilization formulation that is thought to increase bioavailability of resveratrol via lymphatic system absorption. Jupiter Neurosciences (formerly Jupiter Orphan Therapeutics;  “Jupiter”) is pursuing the use of resveratrol in mucopolysaccharidosis type 1 (MPS 1), Friedreich’s Ataxia, and Alzheimer’s Disease/Mild Cognitive Impairment.

This paper describes a first in human study (FIH) to evaluate the bioavailability of resveratrol after ascending, single oral doses up to 700 mg resveratrol as JOTROLTM. After a single 500 mg dose of JOTROLTM, a Cmax of 455 ng/mL was observed, vs. 85 ng/mL Cmax after a 1g encapsulated dose[2]and 1942 ng/mL after a 2.5 g micronized dose[3]. In this study, resveratrol exposures (AUCs and Cmax) increased with increasing doses. This increase appears to be higher than dose-proportional for AUC0-t and Cmax. Resveratrol and its three major conjugates accounted for 40 to 55% of the dose in urine, consistent with a high extent of absorption, but <1% of drug related material was intact relative to key metabolites in plasma and urine. Studies in Alzheimer’s patients and in MPS 1 are currently in development to test the effect this improved bioavailability has on those patient populations. (Clintrials.gov, NCT04668274, 12/16/2020, https://clinicaltrials.gov/ct2/show/NCT04668274).

Marshall A. Hayward, Ph.D.
Jupiter Neuroscience Inc. 

David J. Wyatt, M.D.
Syneos Health, Miami, FL USA

 

The Clinical Study aspects of this report were supported by a research grant from the US National Institute on Aging, Grant 1 R44 AG067907-01A1.

Acknowledgment statement for any data distributed by NIAGADS:

Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer's Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging.

For investigators using Safety and pharmacokinetics of a highly bioavailable resveratrol preparation data:

The Clinical Study aspects of this report were supported by a research grant from the US National Institute on Aging, Grant 1 R44 AG067907-01A1.

Kemper C, Benham D, Brothers S, Wahlestedt C, Volmar CH, Bennett D, Hayward M. Safety and pharmacokinetics of a highly bioavailable resveratrol preparation (JOTROL TM). APPS Open. 2022. doi: 10.1186/s41120-022-00058-1.PMID: 35789594