Fetal hepatic function: the disposition of propranolol in the pregnant sheep.

The placental transfer, and maternal and fetal disposition, of the beta-adrenoreceptor blocking drug propranolol were studied in the pregnant sheep near term. In separate studies, propranolol (1 mg/kg) was administered peripherally or into the portal vein as an i.v. bolus, to either mother or fetus. Both mother and fetus were provided with vascular and bile duct cannulae, enabling plasma concentrations and biliary excretion of the drug to be measured over 6 hours. Placental transfer of propranolol was rapid and bidirectional. Comparison of the systemic blood levels obtained after peripheral and portal dosage indicated that hepatic extraction was much more efficient in the adult. This was supported by an apparent/true biliary clearance ratio of approximately 20 in the adult, and only 2-3 in the fetus. These studies show that the fetus near term is exposed to propranolol administered to the mother at a time when its ability to clear the drug is not fully developed.