Source
Division of Neonatology, Clinical Pharmacology and Toxicology, The Pediatric Pharmacology Research Unit Network (PPRU) at Wayne State University, Children's Hospital of Michigan, Detroit, MI, USA. mariateresa.ambat@ttuhsc.edu
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(-1) for IBU and 100 and 200 mg l(-1) 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(-1) 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.