Studies on albumin binding properties in pregnancy and early infancy : with special reference to maternal sulphasalazine treatment

Sammanfattning: Sulphasalazine (SASP) has been avoided during the later part of pregnancy and during breast-feeding as some sulphonamides possess the ability to displace bilirubin from albumin and thus increase the risk of bilirubin-induced brain damage in jaundiced neonates. However, withdrawal of SASP in a woman with ulcerative colitis would mean a cqnsiderable risk of relapse of her disease.In this study, SASP and its metabolite sulphapyridine (SP) was shown to pass the placenta. Sulphapyridine but not SASP appeared in breast-milk, although concentrations in breast-fed infants were low. The substances were eliminated slower in newborns than in adults.The possible bilirubin-displacing effect of SASP and SP was evaluated by using the MADDS (monoacetyldiaminodiphenyl sulphone) method to determine the binding 'properties of serum albumin.MADDS is used as a deputy ligand for bilirubin. In vivo and in vitro studies, using the MADDS and the peroxidase methods, showed that SASP and SP in pharmacological concentrations did not displace bilirubin from albumin.During that study it was noted that the reserve albumin concentration for MADDS was far lower in women at delivery than in non-pregnant women. In a longitudinally followed group of pregnant women, the reserve albumin concentration was gradually lowered during pregnancy, reaching 530/o of the concentration in non-pregnant women at term. This can have pharmacokinetic effects on those drugs that share the binding function on albumin with MADDS and bilirubin. The reduction of the reserve albumin concentration was due to a reduced albumin concentration during pregnancy but also to a reduced binding ability of the albumin molecule.