Absorption, Distribution, Metabolism and Excretion of 14 C-Vatiquinone in Rats, Dogs and Human Subjects.

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, 14 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 14 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.