Protein Binding and Bilirubin Displacing Properties of Bumetanide and Furosemide

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Abstract
We evaluated the protein binding and comparative bilirubin displacing properties of bumetanide and furosemide in pooled adult and cord serum by ultrafiltration (UF), difference spectra (DS), and Sephadex Gel‐25 (SG‐25) filtration. By UF, bumetanide was found to be highly protein bound (96.7 per cent), similar to published data on furosemide (97.2 per cent). SG‐25 filtration and DS showed an equal shift to the left of the free bilirubin curve when bumetanide and furosemide were added to serum, in adult and cord, at equimolar concentrations and both shifted the free bilirubin curve equally. Bilirubin displacement was greater (P < 0.001) in cord than in adult serum with both drugs. When “presumed therapeutic” plasma concentration of furosemide (1–2 mg/liter) and bumetanide (0.5 mg/liter) were compared, it was noted that bumetanide displaced significantly less (P < 0.001) bilirubin from albumin in cord blood than furosemide. Hence, bumetanide displaces less bilirubin at “presumed therapeutic” plasma concentrations than furosemide, suggesting that it might be more prudent to use bumetanide in sick neonates with hyperbilirubinemia. Data also provide evidence that bilirubin displacement by both diuretics is greater in neonatal serum albumin than in the adult.