Nourianz: which tox species, and why?

“The target organs for istradefylline in rats and dogs are consistent and are the adrenal gland (hypertrophy/hyperplasia) and lung (pneumonitis with septal thickening).”

“In human studies, MI was the primary metabolite and no novel metabolites were identified when compared to the rat and dog data.”

“Brain mineralization was not detected in mice administered istradefylline (0, 25, 125, or 250 mg/kg/day) orally for two years or in dogs administered istradefylline (0, 10, 30, or 100 mg/kg/day) orally for 52 weeks.”

“The target organs for istradefylline in rats and dogs are consistent and are the adrenal gland (hypertrophy/hyperplasia) and lung (pneumonitis with septal thickening).”

“The NOAEL is 160 mg/kg/d for this rat fertility study. A rabbit embryo-fetal study was conducted in combination with levodopa/carbidopa.”

“In lifetime oral carcinogenicity studies, there was no evidence of carcinogenicity in mouse (0, 25, 125, or 250 mg/kg) or rat (0, 30, 100, or 320 mg/kg).”

“Brain mineralization was not detected in mice administered istradefylline (0, 25, 125, or 250 mg/kg/day) orally for two years or in dogs administered istradefylline (0, 10, 30, or 100 mg/kg/day) orally for 52 weeks.”