PERINATAL AND POSTNATAL STUDY OF TRANDOLAPRIL (RU44570) IN RATS

A perinatal and postnatal study was performed in female Sprague-Dawley rats treated orally with trandolapril (RU44570) at dosage levels of 3, 30 and 300 mg/kg/day from day 17 of pregnancy to postpartum day 21. In each group, 24 or 25 pregnant female rats were allowed to litter naturally for the postnatal examination of their offspring. Clinical symptoms and mortality attributable to the administration of RU44570 were not observed in the dams (P). In the 30 and 300 mg/kg group, food consumption was slightly lower than that of the control group during the lactation period, however RU44570 did not affect body weight gain. Incidence of dilatation of renal pelvis with higher value in kidney weight was increased in offspring (F1) in the 30 and 300 mg/kg dosage groups, and water consumption at the same dosage groups was higher than that of the control group. Body weight gain in offspring (F1) was depressed in each treated group and viability of offspring (F1) from postpartum day 0 to day 4 was slightly decreased in the 30 and 300 mg/kg dosage groups comparing with that of the control group. No adverse effects were observed on the other postnatal development of the offspring, such as differentiation, sexual maturation, reflex, motor activity, emotionality, learning ability and reproductive performance. No adverse effects were detected in the second generation offspring (F2). The results suggest that the non-effective dose of RU44570 is 3 mg/kg for dams (P), lower than 3 mg/kg for development in offspring and 300 mg for fetuses (F2), respectively.