Exxua: genotox, carcinogenicity and repro: done or skipped?

“Gepirone HCl tested negative in 4 genotoxicity assays (Ames, in vivo rat micronucleus, hepatocyte DNA repair, and CHO/HGPRT mammalian gene mutation assays) and in a chromosome aberrations assay conducted in CHO cells with 5 hours treatment.”

“This reviewer agreed with the Sponsor that there were no gepirone-related tumors evident in either rats or mice up to maximum tolerated doses (MTD); concurrence by the Executive-CAC was given on January 8, 2002.”

“In embryo/fetal development studies, oral administration of gepirone to pregnant rats (75, 150, and 300 mg/kg/day) or pregnant rabbits (50, 100, and 200 mg/kg/day) during the period of organogenesis resulted in decreased embryo/fetal body weights and lengths, with accompanying skeletal variations, at the mid and high doses.”

“Convulsions were occasionally noted in some general toxicology studies, and gepirone lowered seizure thresholds for strychinine and picrotoxin in rats. Acute cardiac effects were reversible and included decreased heart rate, mean arterial pressure, and contractility, with no apparent alterations in EKG parameters.”