Placental transfer of indomethacin in the rabbit and sheep

The placental transfer of indomethacin was studied in the rabbit at 30 days of gestation and in the sheep between 120 and 135 days of gestation. Plasma concentrations of indomethacin reached a maximum of 13.7 +/- 1.6 and 10.9 +/- 1.5 microgram/mL in the doe and fetuses, respectively, at 1 h following a maternal subcutaneous injection of 10.0 mg/kg. The maternal plasma concentration of drug decreased rapidly but the fetal plasma concentration of drug remained elevated and exceeded that of the doe before decreasing. Indomethacin became detectable in the amniotic fluid after 2 h, reached a maximum of 3.2 +/- 0.8 microgram/mL at 4 h, and the gradually decreased. The intravenous infusion of 10.0 mg of indomethacin per kilogram over 30 min into a pregnant ewe resulted in a maximal plasma concentration of 13.5 +/- 0.7 microgram/mL in the ewe and 0.6 +/- 0.1 microgram/mL in the fetus at the termination of the infusion. The concentration of indomethacin in the amniotic fluid increased to a maximum of 3.5 +/- 0.5 microgram/mL 150 min after the infusion stopped. There was an increase in the percentage of drug bound by the fetal plasma proteins as gestation advanced. Thus, there exists the possibility that the fetus would be exposed to increasing amounts of indomethacin as term approached.