FERTILITY STUDY OF TRANDOLAPRIL (RU44570) IN RATS

A fertility study was performed in Sprague-Dawley rats treated orally with trandolapril (RU44570) at the dosage levels of 3, 30 and 300 mg/kg/day. The male rats were treated for 63 days before mating and during the mating period. The female rats were treated from 14 days before mating to day 7 of pregnancy. Each 24 male and female rats in the same dosage group were mated and female rats were sacrificed on day 20 of pregnancy for the examination of their fetuses. No abnormal findings were observed in symptom during the administration period, however body weight gain and food consumption in both male and female animals of treated groups were lower than control group. Any adverse effects on reproductive performance were not detected. Numbers of implantations and live fetuses were decreased slightly at 30 and 300 mg/kg dosage group comparing with those of the control group. However, RU44570 did not affect fetal mortality, growth of fetuses, or the incidence of external, visceral or skeletal malformation of the fetuses. From these results, it is suggested that non-effective dose level of RU44570 is lower than 3 mg/kg for general toxicity in parent animals, 300 mg/kg for reproductive ability in parent animals, and 3 mg/kg for development in embryos and fetuses, respectively.