Placental transfer of ritodrine hydrochloride in sheep

Abstract
The purpose of this study was to examine the placental passage of ritodrine hydrochloride in relation to the drug's effects on the fetal circulation. Studies were carried out on nine nulliparous pregnant (120–140 days) ewes with chronically implanted cannulae for measurements of maternal and fetal arterial pressures and for blood sampling. One group of animals received sequential infusions of doses ranging from 0.1 to 30 μg/kg per min for 30 min (group 1). A second group was given a constant infusion of the drug at a dose of 3.0 μg/kg per min for 4 h (group 2). The peak concentrations of ritodrine in maternal and fetal blood were determined by radioimmunoassay. In group 1 they were 313.4 ± 24.1 ng/ml (mean ± S.E.) and 12.6 ± 3.7 ng/ml at the finish of 30.0 μg/kg per min infusion for maternal and fetal blood, respectively. In group 2, maternal drug levels were 81.3 ± 20.4 ng/ml after 30 min and 95.9 ± 17.1 ng/ml after 4 h of the infusion. Fetal plasma concentrations increased slowly from trace levels at 30 min to 3.3 ± 0.7 ng/ml at 4 h. Fetal blood pressure and heart rate did not show any significant changes during and after the infusion of ritodrine in both treatment groups. Our findings demonstrate the maternal administration of ritodrine produces no significant effects on the circulatory system of the fetal lamb because of the low transplacental passage of this drug.

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