Placental transfer of the thromboxane synthetase inhibitor ridogrel in thelate-pregnant ewe

Objectives: To assess the occurrence of placental transfer of the thromboxa ne synthetase inhibitor ridogrel in the pregnant ewe and to determine its e ffect on prostanoid levels in the ewe and fetal lamb, on uterine contractil ity and on maternal and fetal hemodynamics. Study design: Five chronically instrumented pregnant ewes at 122 days of gestation received intravenous in fusions of 5 mg/kg/3 h ridogrel and solvent. Maternal and fetal arterial sa mples were obtained at predetermined intervals to determine concentrations of ridogrel and prostaglandin metabolites TXB2, 6-keto-PGF(1)alpha, PGF(2)a lpha, and PGE(2). Maternal and fetal responses of blood flow and pressures were determined. Results: Fetal ridogrel levels were 25% of maternal concen trations. Ridogrel showed rapid and marked thromboxane synthetase inhibitio n and augmentation of levels of prostaglandin metabolites. There was no evi dence of change in amniotic pressure, uterine blood flow, maternal and feta l blood pressure and heart rate. Conclusion: Ridogrel is a potent thromboxa ne synthetase inhibitor which passes the sheep placenta, does not influence maternal and fetal hemodynamics and uterine contractility, and shows simil ar antiplatelet activity in the ewe and the fetal lamb. (C) 1999 Elsevier S cience Ireland Ltd. All rights reserved.