Absorption, distribution, metabolism and excretion of 14 C-vatiquinone in rats, dogs, and human subjects

• Published in: Xenobiotica Vol. 53; no. 5; pp. 396 - 411
• Main Authors: Ma, Jiyuan, Lee, Lucy, Yao, Bert, Giannousis, Peter, Thoolen, Martin, Ye, Qing, Golden, Lee, Klein, Matthew, Kong, Ronald
• Format: Journal Article
• Language: English
• Published: England 08.08.2023
• Subjects: metabolism; vatiquinone; excretion; distribution; PTC743; absorption
• ISSN: 0049-8254; 1366-5928
• DOI: 10.1080/00498254.2023.2245459

Vatiquinone is a potent inhibitor of 15-lipoxygenase and is in clinical development for the treatment of mitochondrial diseases and other disorders characterized by high levels of oxidative stress and dysregulation of energy metabolism.In rats, C-vatiquinone-derived radioactivity was quickly and widely distributed throughout the body and cleared from most tissues by 24 h post-dose following a single oral dose of C-vatiquinone.Following oral administration, 94% of dose was recovered within 7 days in rats, approximately 61% of dose was recovered within 7 days in dogs and approximately 93% of dose was recovered within 9 days in human subjects (IND 119220). Faecal excretion was the major route (>56% dose) in all species; urinary excretion was minimal in rats and dogs (<3% dose) but was higher in humans (∼ 22% dose).Following oral administration, vatiquinone was the dominant circulating component in rats and dogs but was minor in human subjects. There were no plasma metabolites that were more than 10% of total drug related exposures in all species.Following oral administration, vatiquinone was not detectable in urine but was the most prominent component in faeces in rats, dogs, and humans.