[The effect of indomethacin on placental permeability and the fetal lung circulation].

Administration of indomethacin, a typical representative agent among the prostaglandin synthetase inhibitors (PGSI) causes contraction of the fetal ductus arteriosus and recently the relationship between these PGSI-type agents and the development of persistent fetal circulation (PFC) has been gaining attention in medical circles. Therefore, we studied the pharmacokinetics of indomethacin and its effect on the fetal lung. 1) Indomethacin (i.v.) was administered to near-term rabbits and its placental passage was studied. As to the chronological changes of this preparation in fetal blood, the maximum concentration and half-life were delayed compared with the changes in maternal blood. The concentration of indomethacin in fetal blood remained constant at around 33 percent irrespective of the doses to the mother and the number of gestational days. 2) When we administered indomethacin (0.5mg X 5 days, s.c.) to pregnant Wistar rats, neonatal findings (after spontaneous delivery) showed death in 7.0% and asphyxia in 10.5% of the neonates. Thus a significantly higher rate of abnormalities was observed in the neonates after spontaneous delivery compared with those delivered by laparotomy. During our histopathological studies of the lungs of the neonates, the complication of emphysema was observed in 2/4 of the dead neonates but no other abnormal findings were made. Hypertrophy of the pulmonary vascular bed in neonatal rats was not observed.