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

Journal of Perinatology volume 28, pages 287–290 (2008)Cite this article

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.

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References

  1. Patel J, Marks KA, Roberts I, Azzopardi D, Edwards AD . Ibuprofen treatment of patent ductus arteriosus. Lancet 1995; 346: 255.

    Article  CAS  Google Scholar 

  2. Varvarigou A, Bardin CL, Beharry K, Chemtob S, Papageorgiou A, Aranda JV . Early ibuprofen administration to prevent patent ductus arteriosus in premature newborn infants. JAMA 1996; 275: 539–544.

    Article  CAS  Google Scholar 

  3. Van Overmeire B, Follens I, Hartmann S, Creten WL, Van Acker KJ . Treatment of patent ductus arteriosus with ibuprofen. Arch Dis Child Fetal Neonatal Ed 1997; 76: F179–F184.

    Article  CAS  Google Scholar 

  4. Van Overmeire B, Smets K, Lecoutere D, Van de Broek H, Weyler J, Degroote K et al. A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med 2000; 343: 674–681.

    Article  CAS  Google Scholar 

  5. Patel J, Roberts I, Azzopardi D, Hamilton P, Edwards AD . Randomized, double-blind controlled trial comparing the effects of ibuprofen with indomethacin on cerebral hemodynamics in preterm infants with patent ductus arteriosus. Pediatr Res 2000; 47: 36–42.

    Article  CAS  Google Scholar 

  6. De Carolis MP, Romagnoli C, Polimeni V, Piersigilli F, Zecca E, Papacci P et al. Prophylactic ibuprofen therapy of patent ductus arteriosus in preterm infants. J Pediatr 2000; 159: 364–368.

    CAS  Google Scholar 

  7. Lago P, Bettiol T, Salvadori S, Pitassi I, Vianello A, Chiandetti L . Safety and efficacy of ibuprofen versus indomethacin in preterm infants for patent ductus arteriosus: a randomized controlled trial. Eur J Pediatr 2002; 161: 202–207.

    Article  CAS  Google Scholar 

  8. Su PH, Chen JY, Su CM, Huang TC, Lee HS . Comparison of ibuprofen and indomethacin therapy for patent ductus arteriosus in preterm infants. Pediatr Int 2003; 45: 665–670.

    Article  CAS  Google Scholar 

  9. Thomas RL, Parker GC, Van Overmeire B, Aranda JV . A meta-analysis of ibuprofen versus indomethacin for closure of patent ductus arteriosus. Eur J Pediatr 2005; 164: 135–140.

    Article  CAS  Google Scholar 

  10. Aranda JV, Thomas R . Systematic review. Intravenous ibuprofen in preterm newborns. Semin Perinatol 2006; 30: 114–120.

    Article  CAS  Google Scholar 

  11. Mosca F . Cerebral vasoactivity to arterial carbon dioxide tension in preterm infants: the effect of ibuprofen. J Pediatr 1999; 135: 644–646.

    Article  CAS  Google Scholar 

  12. Pezzati M, Vangi V, Biagiotti R, Bertini G, Cianciulli D, Rubartelli FF . Effects of indomethacin and ibuprofen on mesenteric and renal blood flow in preterm infants with patent ductus arteriosus. J Pediatr 1999; 135: 733–738.

    Article  CAS  Google Scholar 

  13. Romagnoli C, De Carolis MP, Pappaci P, Polimeni V, Luciano R, Peirsigilli F et al. Effects of prophylactic ibuprofen on cerebral and renal hemodynamics in very preterm neonates. J Clin Pharm Ther 2000; 67: 676–683.

    Article  CAS  Google Scholar 

  14. Walker PC . Neonatal bilirubin toxicity: a review of kernicterus and the implications of drug-induced bilirubin displacement. Clin Pharmacokinet 1987; 13: 26–50.

    Article  CAS  Google Scholar 

  15. Brodersen R, Friis-Hansen B, Stern L . Drug-induced displacement of bilirubin from albumin in the newborn. Dev Pharmacol Ther 1986; 6: 217–229.

    Article  Google Scholar 

  16. Cashore WJ, Gartner LM, Oh W, Stern L . Clinical application of bilirubin binding determinations: current status. J Pediatr 1978; 93: 827–833.

    Article  CAS  Google Scholar 

  17. Robertson A, Karp W, Brodersen R . Bilirubin displacing effects of drugs used in neonatology. Acta Pediatr Scand 1991; 80: 1119–1127.

    Article  CAS  Google Scholar 

  18. Cooper-Peel C, Brodersen R, Robertson A . Does ibuprofen affect bilirubin-albumin binding in newborn infant serum? Pharmacol Toxicol 1996; 79: 297–299.

    Article  CAS  Google Scholar 

  19. Aranda JV, Varvarigou A, Beharry K, Bansal R, Bardin C, Modanlou H et al. Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant. Acta Pediatr 1997; 86: 289–293.

    Article  CAS  Google Scholar 

  20. Odell GB . Neonatal Hyperbilirubinemia. Monographs in Neonatology. Grune &Stratton Inc.: New York, 1980, pp 137–142.

    Google Scholar 

  21. Odell GB, Cohen SN, Kelly PC . Studies in kernicterus II: the determination of the saturation of serum albumin with bilirubin. J Pediatr 1969; 74: 214–230.

    Article  CAS  Google Scholar 

  22. Jacobsen J, Wennberg RP . Determination of unbound bilirubin in the serum of newborns. Clin Chem 1974; 20: 783–789.

    CAS  PubMed  Google Scholar 

  23. Ostrea EM, Bassel M, Fleury C, Bartos A, Jesurun CA . Influence of free fatty acids and glucose infusion on serum bilirubin and bilirubin binding to albumin: clinical implications. J Pediatr 1983; 102: 426–432.

    Article  Google Scholar 

  24. van Overmiere B, Ahlfors CE . The influence of ibuprofen-lysine on unbound bilirubin plasma levels in preterm neonates. Pediatr Res 2004; 55: 474A.

    Google Scholar 

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Author notes

  1. M T C Ambat

    Present address: 2Current address: MTC Ambat, Texas Tech University Health Sciences Center, El Paso, Texas, USA.,

Authors and Affiliations

  1. 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

    M T C Ambat, E M Ostrea Jr & J V Aranda

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  1. M T C Ambat
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Ambat, M., Ostrea, E. & Aranda, J. Effect of ibuprofen L-lysinate on bilirubin binding to albumin as measured by saturation index and horseradish peroxidase assays. J Perinatol 28, 287–290 (2008). https://doi.org/10.1038/sj.jp.7211925

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