Fixed Drug Combinations and the Displacement of Bilirubin from Albumin

Abstract
Silverman and associates,1 reported that the use of sulfisoxazole (Gantrisin) in premature infants resulted in the occurrence of kernicterus at low levels of serum bilirubin. Odell2 subsequently demonstrated that sulfisoxazole displaces bilirubin from its albumin binding sites in vitro, thereby making available lipid soluble free bilirubin capable of penetrating the central nervous system. This effect of sulfisoxazole in producing kernicterus has been confirmed experimentally in vivo in rats.3 Odell4 and Khanna, et al.5 have demonstrated a similar but quantitatively even greater bilirubin displacing effect of caffeine sodium benzoate, a drug still recommended by some as a respiratory stimulant for the newborn.
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