Placental transfer of sulindac, sulindac sulfide, and indomethacin in a human placental perfusion model, ,

Objective: Evaluation of the transplacental transfer and placental metabolism of sulindac, its active sulfide metabolite, and indomethacin, drugs used as tocolytic agents, in dual recirculating human placental perfusion. Study Design: Term placentas were obtained with maternal consent immediately after delivery. Drugs were added to the maternal reservoir, together with antipyrine as a reference compound, and disappearance from the maternal circulation and appearance in the fetal circulation were followed up for 2 hours in 4 experiments for each compound. Drug concentrations were analyzed by high-performance liquid chromatography. Results: The fetal/maternal concentration ratios after 2-hour perfusions were 0.34 ± 0.19 (mean ± SD, sulindac), 0.54 ± 0.17 (sulfide), and 0.45 ± 0.16 (indomethacin), and the fetal-maternal transfer percentages at 2 hours were 11.6 ± 5.9 (sulindac), 18.2 ± 5.2 (sulfide), and 15.3 ± 4.5 (indomethacin). No metabolism of sulindac or indomethacin was detected. Conclusion: Sulindac sulfide, formed through hepatic metabolism, reaches the fetus in higher concentrations than does sulindac or indomethacin. Neither sulindac nor indomethacin is metabolized by the human placenta. (Am J Obstet Gynecol 1999;180:174-80.)