Candoxatril, a prodrug for candoxatrilat, a selective inhibitor of neutral endopeptidase, was administered orally to groups of 24 female rats at doses of 0, 120, 400 or 1200 mg/kg/day from gestation day 6 to lactation day 21 to assess effects in pre- and postnatal development of F
1 offspring. All dams were allowed to litter and to raise their F
1 offspring until lactation day 21. The F
1 offspring were examined for postnatal developmental indices, reflex behaviors and memory. A functional observational battery(FOB)was also conducted. A marked increase in spontaneous activity of the dams was observed in all condoxatril-treated groups. Maternal body weight gain was decreased in the 400 and 1200 mg/kg/day groups during the treatment periods. No significant differences were found for reproductive parameters. The male and female pups in the 1200 mg/kg/day group had significantly lower body weights beginning on postnatal days 21 and 14, respectively, through to the end of the study. There were no drug-related effects on pre- and postnatal developmental indices, FOB, sensory function tests or memory test. The no observed adverse effect levels were 120 and 400 mg/kg/day for the F
0 dams and F
1 offspring, respectively.
View full abstract