1. Safety, tolerability, and pharmacokinetics of repeated oral doses of 2-hydroxybenzylamine acetate in healthy volunteers: a double-blind, randomized, placebo-controlled clinical trial.
- Author
-
Pitchford, Lisa M., Driver, Patricia M., Fuller, John C., Akers, Wendell S., Abumrad, Naji N., Amarnath, Venkataraman, Milne, Ginger L., Chen, Sheau-Chiann, Ye, Fei, Roberts II, L. Jackson, Shoemaker, M. Benjamin, Oates, John A., Rathmacher, John A., and Boutaud, Olivier
- Subjects
PHARMACOKINETICS ,CLINICAL trials ,MILD cognitive impairment ,ACETATES ,VOLUNTEERS ,CEREBROSPINAL fluid ,BUSULFAN - Abstract
Background: 2-Hydroxybenzylamine (2-HOBA) is a selective dicarbonyl electrophile scavenger being developed as a nutritional supplement to help protect against the development of conditions associated with dicarbonyl electrophile formation, such as the cognitive decline observed with Mild Cognitive Impairment or Alzheimer's disease. Methods: This study evaluated the safety, tolerability, and pharmacokinetics of repeated oral doses of 2-HOBA acetate (500 or 750 mg) administered to healthy volunteers every eight hours for two weeks. The effects of 2-HOBA on cyclooxygenase function and cerebrospinal fluid penetrance of 2-HOBA were also investigated. Results: Repeated oral administration of 2-HOBA was found to be safe and well-tolerated up to 750 mg TID for 15 days. 2-HOBA was absorbed within 2 h of administration, had a half-life of 2.10–3.27 h, and an accumulation ratio of 1.38–1.52. 2-HOBA did not interfere with cyclooxygenase function and was found to be present in cerebrospinal fluid 90 min after dosing. Conclusions: Repeated oral administration of 2-HOBA was found to be safe and well-tolerated. These results support continued development of 2-HOBA as a nutritional supplement. Trial registration: Studies are registered at ClinicalTrials.gov (NCT03555682 Registered 13 June 2018, NCT03554096 Registered 12 June 18). [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF