RESUMO
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.
