Developmental Toxicity Studies in Mice, Rats, and Rabbits with the Anticonvulsant Gabapentin

The developmental toxicity of the anticonvulsant agent gabapentinwas evaluated in mice, rats, and rabbits treated by gavage throughoutorganogenesis. Mice received 500, 1000, or 3000 mg/kg on gestationdays (GD) 6–15 and rats and rabbits received 60, 300,or 1500 mg/kg on GD 6–15 (rats) or 6–18 (rabbits).Additional groups received an equivalent volume of the vehicle,0.8% methylcellulose, or remained untreated. All dams were observeddaily for clinical signs of toxicity. In mice, body weightsand food consumption were recorded on GD 0, 6, 12, 15, and 18while in rats and rabbits these parameters were evaluated daily.Near term (mouse, GD 18; rat, GD 20; and rabbit, GD 29) eachfemale was euthanatized, necropsies were performed, and litterand fetal data were collected. Live fetuses were examined forexternal, visceral, and skeletal variations and malformations.No adverse maternal or fetal effects were observed in mice orrats given doses up to 1500 or 3000 mg/kg, respectively. Notreatment-related maternal or fetal effects were apparent inrabbits given 60 or 300 mg/kg. At 1500 mg/kg, one rabbit died,four others aborted, and reduced food consumption and body weightgain were observed. No other reproductive, litter, or fetalparameters were affected, except that the incidence of visceralvariations in rat fetuses was slightly but statistically significantlyincreased at 1500 mg/kg due to a slight increase in the incidenceof dilated renal pelvis. This finding was not considered biologicallysignificant because this degree of variability has been seenin this strain of rats. In conclusion, no evidence of teratogenicitywas found for gabapentin at doses up to 3000 mg/kg in the mouseand up to 1500 mg/kg in the rat and rabbit.