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 doseand 1942 ng/mL after a 2.5 g micronized dose. 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).
There are 3 study reports available with this dataset:
- Plasma levels of resveratrol and 3 key metabolites- a table from the complete clinical study report that contains Measured Values of Resveratrol, Resveratrol Sulfate, Resveratrol 3-Glucuronide and Resveratrol 4-Glucuronide in Human Plasma Samples.
- Urinary excretion data of resveratrol and 3 key metabolites- a table from the complete clinical study report that contains Measured Values of Resveratrol, Resveratrol Sulfate, Resveratrol 3-Glucuronide and Resveratrol 4-Glucuronide in Human Urine Samples.
- PK summary statistics in plasma and urine- a table from the complete clinical study report that contains Descriptive Statistics of Plasma Pharmacokinetic Parameters by Treatment for JOTROL (Resveratrol) and Metabolites – PK Population.
|Suppl_1_plasma, Suppl_2_urine, and Suppl_3_PK_Summary||fsa000043||NG00133.v1||Plasma, Urine and PK Summary|
View the File Manifest for a full list of files released in this dataset.
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.
Use the study-specific acknowledgement statements below (as applicable):
For investigators using any data from this dataset:
Please cite/reference the use of NIAGADS data by including the accession NG00133.
Kemper C,, et al. Safety and pharmacokinetics of a highly bioavailable resveratrol preparation (JOTROL TM). APPS Open. 2022. doi: 10.1186/s41120-022-00058-1.Pubmed Link