STUDIES ON REPRODUCTIVE TOXICITY OF ILOPROST IN RATS, RABBITS AND MONKEYS

A reproduction toxicological test program was performed with the carba prostacyclin derivative iloprost, an analogue to the endogenous prosta cyclin PGI(2), in order to detect possible effects on fertility and re productive performance, on preimplantational, embryonal and fetal deve lopment, on delivery as well as on lactation and postpartum developmen t. While in humans iloprost is administered as an i.v. infusion for 6 h/day, it was administered i.v. to rats, rabbits and monkeys by contin uous infusion with a subcutaneously implanted pump. No influence on ma ting or reproductive parameters was found after treatment of male or f emale rats during the premating phase up to day 7 post coitum (p.c.). Embryonal and fetal development were not remarkably impaired in rabbit s or monkeys after treatment throughout the period of organogenesis. T he only remarkable observations in the embryotoxicity and peri-/postna tal studies in the rat were defects on the digits (reductions of phala ngeal structures) in single individuals. These malformations were inte rpreted as resulting from a compound-related hypotonia with subsequent change in the regional blood flow and the consequence of temporary im pairments of placental blood supply leading to hypoxia in the affected structures.