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  • Title: Placental transfer of SR49059 in the human dually perfused cotyledon in vitro.
    Author: Lagrange FJ, Brun JL, Clot PF, Leng JJ, Saux MC, Kieffer G, Bannwarth BG.
    Journal: Placenta; 2001 Nov; 22(10):870-5. PubMed ID: 11718575.
    Abstract:
    SR49059 is an antagonist of vasopressin V(1a)receptors currently developed as a tocolytic drug. We investigated the transplacental transfer of SR49059 in vitro using the single pass dually perfused human cotyledon model. Thirteen placentae were collected from normal term pregnancies immediately after delivery. The placental transfer of SR49059 was tested at steady state at three different concentrations (100 ng/ml, 200 ng/ml and 500 ng/ml) along with that of antipyrine 20 mg/l as a reference substance. Concentrations were assayed by liquid chromatography with UV (antipyrine) or mass spectrometry (SR49059) detection. At steady state, the mean+/-s.d. fetal transfer rate of SR49059 was 10.80+/-4.33 per cent, 9.34+/-4.41 per cent, and 11.78+/-3.26 per cent at 100 ng/ml, 200 ng/ml and 500 ng/ml, respectively. The corresponding clearance indices were 0.29+/-0.14, 0.25+/-0.08, and 0.31+/-0.06, respectively. The absence of saturation kinetics is consistent with a passive mechanism of transfer. Moderate amounts of SR49059 are transferred from the maternal to the fetal circulation. The clearance index of SR49059 appeared to be very similar to that of ritodrine, which is currently used as a tocolytic.
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