Metabolism and disposition of ritodrine in a pregnant baboon

Relatively little is known about the detailed metabolism of ritodrine. The aim of this study was to examine ritodrine metabolism and pharmacokinetics in the maternal and fetal baboon. A fetal-maternal model was made with use of Papio anubis at 144 days of gestation. Tritiated ritodrine was injected as an intravenous bolus into the mother. Maternal and fetal blood samples, amniotic fluid, and maternal urine were collected at time intervals. Samples were analyzed by a combination of high-pressure liquid chromatography and radiochromatography. Conjugated metabolites were recovered and characterized by cleavage studies with use of beta-glucuronidase and sulfatase. The distribution half-life of ritodrine in the mother was 6 minutes and the elimination half-life was 61 minutes. Metabolites were found in both fetal serum and amniotic fluid. The concentrations of ritodrine and its metabolites in fetal serum were at or above the concentrations in maternal serum at 2 hours after maternal intravenous injection. The principal metabolite identified was the sulfate conjugate. The fetus appears to accumulate metabolites. These data indicate that ritodrine crosses the placenta and, in the baboon, achieves levels in the fetus equal to or higher than those in the mother.