Exxua: which tox species, and why?

“Repeated-dose toxicology studies of adequate duration and at MTDs were performed in rats and dogs.”

“In humans, 2 major metabolites of gepirone have been identified: 1-PP (which is also a metabolite of buspirone, currently approved and marketed as an anxiolytic) and 3’-OH-gepirone. Both of these metabolites have been identified and found to be present in substantial amounts (many times the levels of gepirone) in plasma of the 2 major species used in the preclinical studies, namely rats and dogs, following gepirone administration.”

“In the 1-year study in dogs (4, 8, and 16 mg/kg/day orally, in a capsule), decreases in body weights (and food consumption at the HD) limited doses.”

“Repeated-dose toxicology studies of adequate duration and at MTDs were performed in rats and dogs.”

“traditional Segment II studies, in rats and rabbits, with oral gavage dosing of pregnant females during the period of organogenesis; and 3) a traditional Segment III study in rats, with oral gavage dosing of pregnant females from late pregnancy through lactation”

“More importantly, there was no evidence of carcinogenic potential in the completed two-year mouse and rat bioassays.”

“Both of these metabolites have been identified and found to be present in substantial amounts (many times the levels of gepirone) in plasma of the 2 major species used in the preclinical studies, namely rats and dogs, following gepirone administration.”