Binding of drugs to plasma proteins of swine during the perinatal period

The binding of ¹⁴C-labeled salicylic acid, pentobarbital, thiopental, barbital and nicotine to plasma of swine was studied as a function of perinatal age by equilibrium dialysis. Binding was studied at several drug concentrations, and three age-related profiles were observed. One profile, exhibited by the binding in plasma of the fetal and newborn pig, was characterized by a rapid increase in binding during the first week postpartum. The age-related increase in binding of salicylic acid was probably a function of the distinct fetal and neonatal hypoalbuminemia occurring in this species at birth and to the rise in albumin concentrations during the first 2 weeks postpartum. The binding of pentobarbital and thiopental presented a second developmental profile, characterized by high fractional binding at low drug concentrations and low binding at high drug concentrations in fetal plasma. This concentration-dependent spread in binding values decreased markedly to attain a pattern similar to that of the adult by the first week postpartum. A third profile, characterized by low fractional binding at all ages, was observed for nicotine and barbital. The biphasic binding profile obtained with pentobarbital and thiopental was probably not related to lipoprotein content of plasma or to interference with binding to albumin caused by the binding of endogenous substances, such as fatty acids or bilirubin.