Reproductive toxicity studies of rentiapril

(2R,4R)-2-(o-Hydroxyphenyl)-3-(3-mercaptopropionyl)-4- thiazolidinecarboxylic acid (rentiapril, SA 446), an orally active inhibitor of angiotensin converting enzyme, was examined for effects upon general reproductive performance, for embryofoetal toxicity and for peri- and postnatal toxicity in the rat at dosages of 0, 20, 100 and 500 mg/kg/d. Embryofoetal toxicity was also examined in the New Zealand White rabbit at dosages of 0, 1, 2 and 4 mg/kg/d. The compound was administered by gastric intubation. Prolonged treatment at 100 and 500 mg/kg/d during the fertility study was associated with some slight depression of body weight gain of males. Body weight gain of females during gestation was significantly depressed at 500 mg/kg/d. There was salivation in both sexes at 500 mg/kg/d and also in males receiving 100 mg/kg/d. Following this prolonged treatment in the fertility study. Fo male and female kidney weights were increased at all dosages. Although there was no obvious effect upon fertility there was an increased incidence of total litter loss at 500 mg/kg/d and mean pup weights to day 21 post partum were reduced at this dosage and at 100 mg/kg/d with delays in the attainment of some of the developmental landmarks. In the rat treatment at 500 mg/kg/d from day 7 to 17 of pregnancy did not adversely effect embryofoetal development. Subsequent development and reproductive performance of the F1 offspring was also unimpaired. During this treatment period signs of salivation were seen at 500 mg/kg/d. Slight retardation of maternal body weight gain was noted at 500 mg/kg/d and at 100 mg/kg/d but not at 20 mg/kg/d.(ABSTRACT TRUNCATED AT 250 WORDS)