Increased mesenteric lymph node plasmablasts at end of dosing (highest at 70 mg/kg), reversible after recovery
“At the end of the dosing period (Day 42) a greater number of plasmablasts were observed in the mesenteric lymph nodes of dose group animals relative to controls with the highest numbers observed in the 70 mg/kg group. Following the recovery period (Day 56) there was no difference in lymph node plasmablasts between controls and dose group animals.”
✓ VerifiedFDA multi-discipline review, p. 55Source ↗
Biodistribution & persistence
Gepirone and/or metabolites cross the placenta; fetal radioactivity similar to maternal plasma
“The amount of radiolabel (gepirone-equivalents per gm) was essentially identical in maternal plasma and total fetus, at all time-points, and very similar for maternal and fetal hearts, whereas maternal liver levels were much (5-24-fold) greater than those in fetal liver. Geprione and/or metabolites crossed the placental barrier from mother to fetus.”
✓ VerifiedFDA pharmacology/toxicology review, p. 43Source ↗
Modality-specific risk
Embryo-fetal and postnatal developmental toxicity
“Based on animal reproduction studies, gepirone has been shown to have adverse effects on embryo/fetal and postnatal development.”
✓ VerifiedFDA multi-discipline review, p. 125Source ↗