Reyvow: which tox species, and why?

“General Toxicology: the oral toxicity of lasmiditan was tested in Sprague-Dawley rat (4-week + 2-week recovery, 13-week + 4-week recovery, and 26-week + 8-week recovery) and Beagle dog (2-week, 4-week + 2-week recovery, 13-week + 4-week recovery, and 39-week + 8-week recovery).”

“In humans, the major circulating metabolites are M8 and[S,R]-M18, which account for 47.5 and 10.5% of drug-related material in circulation. Both metabolites were produced in mouse, rat, rabbit, and dog.”

“In rat, lasmiditan was administered at doses up to 100 (4-week study) or 200 (13- and 26-week studies) mg/kg/day.”

“General Toxicology: the oral toxicity of lasmiditan was tested in Sprague-Dawley rat (4-week + 2-week recovery, 13-week + 4-week recovery, and 26-week + 8-week recovery) and Beagle dog (2-week, 4-week + 2-week recovery, 13-week + 4-week recovery, and 39-week + 8-week recovery).”

“A standard battery of reproductive and developmental toxicology studies was conducted for lasmiditan (fertility and early embryonic development in male and female Sprague-Dawley rat; embryofetal development in Sprague-Dawley rat and New Zealand White rabbit; pre- and postnatal development in Sprague-Dawley rat).”

“The carcinogenic potential of orally-administered lasmiditan was tested in a 26-week study in Tg.rasH2 mice (0, 20, 50, or 150 mg/kg/day in males; 0, 25, 80, or 250 mg/kg/day in females) and in a 2-year study in rats (0, 10, 25, or 75 mg/kg/day).”

“Binding affinity was similar among mouse, rat, rabbit, dog, and human 5-HT1F receptors.”