Quantitative Contribution of Endogenous Compounds and Hypoalbuminemia in Reducing the Binding of Furosemide in the Plasma of Newborn Infants

Abstract

The protein binding of furosemide was studied in the plasma of newborn infants and adult subjects. Plasma consisted of two pools obtained from 25 newborns and adult subjects. The concentrations of albumin were 36.8 (newborn) and 48.3 g/l (adult). The unbound fraction of furosemide was 1.38 +/- 0.15 (adult) and 2.03 +/- 0.13% (newborn; p < 0.001). After extensive dialysis of the plasma, the unbound fraction of furosemide was 1.12 +/- 0.15 (adult) and 1.39 +/- 0.09% (newborn; p < 0.0001), suggesting that dialyzable endogenous compounds interfere with the binding of furosemide. The addition of human albumin to the newborn plasma to give a final albumin concentration of 48.3 g/l yielded an unbound fraction of furosemide of 1.63 +/- 0.08 (nondialyzed plasma) and 1.17 +/- 0.08% (dialyzed plasma; p < 0.0001). The addition of albumin to the dialyzed newborn plasma, to give a final albumin concentration similar to that in adult plasma, decreased the unbound furosemide to the level of the dialyzed adult plasma. The binding defect of furosemide in newborn plasma reflects either the effects of the endogenous inhibitors or of hypoalbuminemia. The intrinsic binding properties for furosemide of newborn dialyzed plasma are similar to those of dialyzed adult plasma. This consideration corroborates our previous results on the binding of furosemide and diazepam, salicylic acid and digitoxin to newborn and adult albumin. The displacement of furosemide by salicylic acid, tolbutamide and azapropazone is 70% greater in newborn than in adult plasma. The greater displacing effect is largely due to hypoalbuminemia.