Effect of drug combinations on bilirubin-albumin binding

Drugs which compete with bilirubin for albumin binding may increase the risk of kernicterus. Fortunately, few drugs are strong competitors. However, in neonatology, many drugs are used simultaneously. We have studied the effect of drug combinations on bilirubin binding using human serum albumin and the peroxidase method. Combinations of aminophylline 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 predicted from each drug's individual effect. These results are consistent with a flexible model of albumin binding. Combinations of drugs which are both albumin-bound and reach high serum concentrations should be tested for their combined effect on bilirubin binding and this information used in deciding on treatment in sick, premature infants.