HUMAN PLACENTAL-TRANSFER OF THE PROSTAGLANDIN INHIBITOR SULINDAC USING AN IN-VITRO MODEL

Objective: We determined whether the prostaglandin inhibitor sulindac crosses the human placenta. Methods: The recirculating single-cotyledon placenta model was used to characterize the maternal-to-fetal and fetal-to-maternal transport of C-14-labeled sulindac in normal term placentas perfused immediately after delivery. Antipyrine was added as a standard for simple diffusion. Serial samples were taken from both reservoirs during each 3-hour perfusion. Transport was calculated using liquid scintillation spectrometry for C-14-labeled sulindac and high-performance liquid chromatography for antipyrine. Results: There was significant maternal-to-fetal transfer of sulindac. The mean (+/- SD) transfer at 2 hours was 7.22 +/- 2.57%. The fetal-to-maternal transfer was similar at 10.75 +/- 3.80%. The mean maternal/fetal concentration ratio of sulindac was 0.42 at 3 hours. Placental uptake ranged from 24-45 ng/g of placenta. Conclusions: Sulindac crosses the human placenta in small but significant amounts. The transport is similar in both directions, implying simple diffusion.