EFFECT OF DRUG-COMBINATIONS ON BILIRUBIN-ALBUMIN BINDING

Drugs which compete with bilirubin for albumin binding may increase th e risk of kernicterus. Fortunately, few drugs are strong competitors. However, in neonatology, many drugs are used simultaneously. We have s tudied the effect of drug combinations on bilirubin binding using huma n serum albumin and the peroxidase method. Combinations of aminophylli ne with phenobarbital, cefotaxime and vancomycin were studied as well as the combination of vancomycin and cefotaxime. The results show that the bilirubin-displacing effect of the drug combinations cannot be pr edicted from each drug's individual effect. These results are consiste nt with a flexible model of albumin binding. Combinations of drugs whi ch are both albumin-bound and reach high serum concentrations should b e tested for their combined effect on bilirubin binding and this infor mation used in deciding on treatment in sick, premature infants.