The Effect of Drugs on Albumin Binding of Bilirubin and on Free Bilirubin Concentration as Determined by Fluorescence Quenching

Abstract

Fluorescence quenching was used to determine the influence of five drugs commonly used in the newborn infant, on the binding of bilirubin to albumin, and to quantitate the resultant changes in binding parameters and the free bilirubin concentration. The five drugs studied were digoxin, furosemide, diazepam, phenytoin sodium, and theophylline. The primary influence of digoxin, furosemide, diazepam, and phenytoin sodium was on the affinity of albumin to bind bilirubin. They also affected the capacity of albumin to bind bilirubin, but to a lesser extent. Furosemide reduced the apparent binding affinity by 60 percent (p = 0.01), phenytoin sodium by 58 percent (p < 0.01), digoxin by 52 percent (p = 0.02), and diazepam by 45 percent (p = 0.03). Furosemide reduced the apparent binding capacity by 24 percent (p < 0.001), digoxin by 23 percent (p = 0.04), and diazepam by 13 percent (p = 0.10). Phenytoin sodium had a different effect on the apparent binding capacity: It increased the apparent capacity by 30 percent (p < 0.01). Theophylline had no significant effects on either binding affinity or capacity or free bilirubin concentration. Furosemide, digoxin, and diazepam significantly increased free bilirubin concentration at all total bilirubin concentrations; therefore, these drugs should be used with caution in the jaundiced newborn infant. Phenytoin sodium increased free bilirubin concentrations in the low total bilirubin ranges only; however, the increase was marginal and unlikely to be clinically significant.