The effects of the administration of fenoprofen or indomethacin to rat dams during late pregnancy, with special reference to the ductus arteriosus of the fetuses and neonates
Powell, J.G.; Cochrane, R.L.
Toxicology and Applied Pharmacology 45(3): 783-796
1978
ISSN/ISBN: 0041-008X PMID: 725931 Document Number: 129384
Examination of a series of normal neonatal rats showed that the ductus arteriosus did not begin closing until approximately 16-20 min after birth and was usually completely closed by 85-98 min after birth. Pregnant rats were orally dosed twice daily for 1.5-5 days with 50 mg/kg of fenoprofen Ca, 1.6 mg/kg of indomethacin or vehicle (1% methylcellulose), beginning 18 days after mating. The fenoprofen Ca treatment resulted in premature (in utero) closure of the ductus arteriosus in 4-10% of the offspring of dams treated for 3.5-5 days. The indomethacin treatment caused premature (in utero) ductal closure in 1-3% of the offspring after 4.5-5 days. Both treatments also caused a high incidence of maternal mortality after 4.5-5 days (38-50% for fenoprofen Ca and 13-25% for indomethacin) and increased the duration of gestation or blocked parturition. Treatment of rat dams with 4 mg of progesterone daily from 18-22 days after mating blocked parturition, but the ductus arteriosus was not closed in any of the fetuses that were retained in utero. The in utero closure of the ductus found in fetuses of dams treated with fenoprofen Ca or indomethacin apparently was not a consequence of retention of the fetuses in the uterus.