Indomethacin--placental transfer, cytotoxicity, and teratology in the rat

Aspirin is a well-known teratogen in laboratory animals and is an inhibitor of prostaglandin synthesis. To further investigate the inhibition of prostaglandin synthesis as a mechanism of teratogenesis, we examined the teratologic potential, cytotoxic potential, and placental transfer of indomethacin in the rat. Indomethacin was not teratologic, not cytotoxic to cells in the embryonic hindlimb bud, and did not cross the placenta in physiologically significant amounts on days 11 to 12 of gestation. Near parturition, however, indomethacin crossed the placenta in pharmacologically significant amounts. The pharmacokinetics of placental drug transfer are discussed.