Cyclooxygenase inhibition reduces placental transfer: reversal by carbacyclin

The effect of the cyclooxygenase inhibitors, indomethacin and ibuprofen, on diffusional transfer in the human placenta was assessed with the dual-perfused isolated placental lobe. Antipyrine, a freely diffusible substance, was used as an indicator of placental transfer efficiency. Each inhibitor (100 mumol/L) was perfused for 30 minutes after a baseline period, resulting in a significant reduction in antipyrine clearance. During a subsequent washout period, ibuprofen-inhibited antipyrine clearance returned to baseline values, whereas indomethacin-inhibited clearance remained reduced. An additional 30 minutes perfusion of 500 mumol/L of ibuprofen resulted in a further reduction in antipyrine clearance compared with 100 mumol/L of ibuprofen, suggesting a dosage-related effect. The perfusion of each inhibitor caused a reduced production of 6-keto-prostaglandin F1 alpha (the stable metabolite of prostacyclin) in the fetal circulation. The simultaneous perfusion of carbacyclin, a prostacyclin analogue, at 100 nmol/L and 1 mumol/L resulted in a dosage-dependent reversal of the effects of ibuprofen (500 mumol/L) on antipyrine clearance. The results indicate that the inhibition of cyclooxygenase activity reduces placental transfer and that the effects of these inhibitors are reversed by carbacyclin. This study suggests that the use of cyclooxygenase inhibitors during pregnancy could compromise the developing fetus by reducing placental transfer.