DEVELOPMENTAL TOXICITY STUDIES IN MICE, RATS, AND RABBITS WITH THE ANTICONVULSANT GABAPENTIN

The developmental toxicity of the anticonvulsant agent gabapentin was evaluated in mice, rats, and rabbits treated by gavage throughout orga nogenesis. Mice received 500, 1000, or 3000 mg/kg on gestation days (G D) 6-15 and rats and rabbits received 60, 300, or 1500 mg/kg on GD 6-1 5 (rats) or 6-18 (rabbits). Additional groups received an equivalent v olume of the vehicle, 0.8% methylcellulose, or remained untreated. All dams were observed daily for clinical signs of toxicity. In mice, bod y weights and food consumption were recorded on GD 0, 6, 12, 15, and 1 8 while in rats and rabbits these parameters were evaluated daily. Nea r term (mouse, GD 18; rat, GD 20; and rabbit, GD 29) each female was e uthanatized, necropsies were performed, and litter and fetal data were collected. Live fetuses were examined for external, visceral, and ske letal variations and malformations. No adverse maternal or fetal effec ts were observed in mice or rats given doses up to 1500 or 3000 mg/kg, respectively. No treatment-related maternal or fetal effects were app arent in rabbits given 60 or 300 mg/kg. At 1500 mg/kg, one rabbit died , four others aborted, and reduced food consumption and body weight ga in were observed. No other reproductive, litter, or fetal parameters w ere affected, except that the incidence of visceral variations in rat fetuses was slightly but statistically significantly increased at 1500 mg/kg due to a slight increase in the incidence of dilated renal pelv is. This finding was not considered biologically significant because t his degree of variability has been seen in this strain of rats. In con clusion, no evidence of teratogenicity was found for gabapentin at dos es up to 3000 mg/kg in the mouse and up to 1500 mg/kg in the rat and r abbit. (C) 1994 Society of Toxicology.