Effect of ibuprofen L-lysinate on bilirubin binding to albumin as measured by saturation index and horseradish peroxidase assays

Abstract

Objective: To demonstrate, in vitro, the influence of increasing ibuprofen (IBU) concentration on bilirubin-albumin (B-A) binding. Study Design:The influence of IBU on B-A binding was measured by saturation index and horseradish peroxidase assays. B-A solutions were prepared at B:A ratios of 0.5, 1.0, 1.5 and 2.0 and bilirubin concentrations of 5 and 10 mg per 100 ml. Drug concentrations used were 142.5, 200 and 285 mg l À1 for IBU and 100 and 200 mg l À1 for acetyl salicylic acid (ASA). Similar tests were performed on premature newborn sera with bilirubin concentrations of 5 to 10 mg per 100 ml.Result: By the saturation index test, significant displacement of bilirubin from albumin with IBU was demonstrated only on B-A solution with high B:A ratio of 2.0 and IBU concentration of 285 mg l À1 and was less as compared to ASA. No displacement was observed in the sera of jaundiced neonates. By the horseradish peroxidase assay using B-A solutions, free bilirubin was significantly increased at (1) increasing concentrations of bilirubin in solution and (2) increasing B:A ratios in a solution containing 5 mg per 100 ml of bilirubin. In the sera of jaundiced neonates, significantly higher free bilirubin concentrations were observed when IBU was added to serum with bilirubin concentration of 10 mg per 100 ml as compared to 5 mg per 100 ml (0.062±0.004 versus 0.026 ± 0.005, P<0.001 by Student's t-test).Conclusion: Displacement of bilirubin was demonstrated only at high IBU concentration and high B:A ratio. However, free bilirubin levels were not shown to increase with increasing IBU concentration.

Disorders of bilirubin binding to albumin and bilirubin-induced neurologic dysfunction

“…Ibuprofen, one of the drugs used for treating patent ductus arteriosus in preterm infants, is a potent bilirubin displacer and has been shown to increase UB concentrations in vitro [21,22]. However, recent in-vivo studies have shown that ibuprofen does not displace bilirubin and increase UB concentrations in preterms with mild to moderate hyperbilirubinemia [23,24].…”

Patent ductus arteriosus in the preterm infant: to treat or not to treat?

“…41,42 In addition, at higher serum concentration ibuprofen can displace bilirubin from its binding to albumin. 38 Indeed, a recent study showed that ibuprofen augments bilirubin toxicity in rat cortical neuronal culture. 43 The clinical significance of this potential neurotoxicity remains unknown.…”

“…[35][36][37] Although ibuprofen appears to have a better profile with regard to renal side effects and organ blood flows, the drug's effect on bilirubin metabolism and displacement of albumin binding, and the possible but recently debated association with pulmonary hypertension, have raised concerns. [38][39][40] Ibuprofen is thought to impair biliary excretion of bilirubin and therefore it raises serum bilirubin level. 41,42 In addition, at higher serum concentration ibuprofen can displace bilirubin from its binding to albumin.…”

Bilirubin Binding Capacity in the Preterm Neonate

“…[73–75] Ahlfors, et al . [74] demonstrated, using the peroxidase method, that a significant increase in UB concentration was only observed at ibuprofen concentrations >50 μg/mL in two pooled newborn sera with BAMRs of 0.3 and 0.36.…”