Developmental Toxicity Studies in Mice, Rats, and Rabbits

The developmental toxicity of the anticonvulsant agent gaba-pentin was evaluated in mice, rats, and rabbits treated by gavage throughout organogenesis. Mice received 500, 1000, or 3000 mg/kg on gestation days (GD) 6-15 and rats and rabbits re-ceived 60, 300, or 1500 mg/kg on GD 6-15 (rats) or 6-18 (rab-bits). Additional groups received an equivalent volume of the vehicle, 0.8 % methylcellulose, or remained untreated. All dams were observed daily for clinical signs of toxicity. In mice, body weights and food consumption were recorded on GD 0, 6, 12, 15, and 18 while in rats and rabbits these parameters were evalu-ated daily. Near term (mouse, GD 18; rat, GD 20; and rabbit, GD 29) each female was euthanatized, necropsies were per-formed, and litter and fetal data were collected. Live fetuses were examined for external, visceral, and skeletal variations and malformations. No adverse maternal or fetal effects were ob-served in mice or rats given doses up to 1500 or 3000 mg/kg, respectively. No treatment-related maternal or fetal effects were apparent 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 gain were observed. No other reproductive, litter, or fetal parameters were affected, except that the inci-dence of visceral variations in rat fetuses was slightly but statis-tically significantly increased at 1500 mg/kg due to a slight in-crease in the incidence of dilated renal pelvis. This finding was not considered biologically significant because this degree of variability has been seen in this strain of rats. In conclusion, no evidence of teratogenicity was found for gabapentin at doses up to 3000 mg/kg in the mouse and up to 1500 mg/kg in the rat an