Bilirubin-Displacing Effect of Ampicillin, Indomethacin, Chlorpromazine, Gentamicin, and Parabens In Vitro and in Newborn Infants

Abstract

□ Displacement of bilirubin bound to human serum albumin by ampicillin, indomethacin, chlorpromazine, gentamicin, methylparaben, and propylparaben was investigated quantitatively. Two methods were used in vitro: measurement of bilirubin displacement by studying the rate of bilirubin oxidation with hydrogen peroxide and peroxidase and determination of the albumin reserve for binding of bilirubin by observation of the dialysis rate of an added trace amount of a deputy ligand monoacetyldapsone (p-acetamido-p'-aminodiphenyl sulfone). The latter method was also used for the determination of the albumin reserve in sera from treated newborn infants. The following doses were given: ampicillin, 100mg/kg iv; indomethacin, 0.2mg/kg iv; chlorpromazine hydrochloride, 0.7mg/kg im; gentamicin sulfate, 2.5mg/kg im. The parabens were present in injectable preparations of chlorpromazine and gentamicin and were therefore given in the following doses: methylparaben, 0.35mg/kg, and propylparaben, 0.05mg/kg. All drugs were given in a single dose. A few additional additives and metabolites were studied in vitro. Ampicillin, given to 19 infants, produced a small, significant decrease in plasma albumin reserve, to 82% of the pretreatment level and, thus, had a slight bilirubin-displacing effect, quantitatively consistent with a weak displacing effect measured in vitro. None of the other substances showed any measurable displacement in vivo, likewise in agreement with the results from in vitro studies.