Bilirubin-displacing effect of furosemide and sulfisoxazole. An in vitro and in vivo study in neonatal serum.

Abstract

Sulfisoxazole and furosemide, 0.1-1.0 mM, both decreased reserve albumin concentration for bilirubin binding in pooled cord serum as estimated by rate of dialysis of 14C-monoacetyl-diamino-diphenylsulfone (MADDS) in undiluted serum at 37 degrees C. Peroxidase oxidation at a bilirubin:albumin ratio of 0.5 also showed that both drugs were capable of displacing bilirubin in vitro when added in molar excess of the albumin present. However, when aliquots of the same treated sera which had been used undiluted in the MADDS assay were diluted 40-fold and titrated with bilirubin and peroxidase, no drug-related increase in free bilirubin or decrease in reserve albumin could be shown. In vivo administration of 1 mg/kg furosemide showed no change in total bilirubin or reserve albumin by the MADDS technique in 8 infants. Estimation of the peak plasma level theoretically achievable with 1 mg/kg of furosemide suggests that peak plasma levels achieved with that dose are probably not high enough to produce significant reduction of reserve albumin, in agreement with the in vivo findings. In testing neonatal serum for bilirubin displacement by drugs, the choice of method, drug concentration, and dilution of the sample may influence the interpretation of results.