Interactions of Bilirubin and Drugs

  • William J. Cashore
  • Masahisa Funato


Many drugs given to mothers and their newborns are bound to albumin. After 25 years of experience in the United States, sulfisoxazole still remains as the only drug clearly associated with an epidemic of kernicterus in newborn infants; however, several other drugs that are often used and most of the newer drugs being developed for possible use in the perinatal period have not been adequately tested for their effects on bilirubin binding, distribution, and metabolism. As the routine use of multiple drugs increases in high-risk newborns, it is appropriate to review the methods available for testing bilirubin-drug interactions. In this presentation we shall review several methods potentially useful for studying bilirubin displacement from albumin by drugs, using examples from our own laboratory.


Albumin Ratio Diamino Diphenyl Sulfone Diphenyl Sulfone Bilirubin Binding Free Bilirubin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    R. C. Harris, J. F. Lucey, and J. R. Maclean, Kernicterus in premature infants associated with low concentrations of bili-rubin in plasma, Pediatrics 21: 875 (1958).PubMedGoogle Scholar
  2. 2.
    R. J. Martinek, Improved micromethod for determination of serum bilirubin, Clin. Chem. Acta 13:161 (1966).CrossRefGoogle Scholar
  3. 3.
    B. T. Doumas, T. Watson, and H. G. Biggs, Albumin standards and the measurement of serum albumin with bromcresol green, Clin. Chem. Acta, 31:87 (1971).CrossRefGoogle Scholar
  4. 4.
    J. Jacobsen and R. P. Wenneberg, Determination of unbound bili-rubin in the serum of newborns, Clin. Chem., 20: 783 (1974).PubMedGoogle Scholar
  5. 5.
    D. Schiff, G. Chan, and L. Stern, Sephadex G-25 quantitative estimation of free bilirubin potential in jaundiced newborn infants’ sera, A guide to the prevention of kernicterus, J. Lab. Clin. Med., 80:455 (1972).PubMedGoogle Scholar
  6. 6.
    G. B. Odell, S. N. Cohen, and P. C. Kelly, Studies in kernicterus. II. The determination of the saturation of serum albumin with bilirubin, J. Pediatr. 74:214 (1969).PubMedCrossRefGoogle Scholar
  7. 7.
    R. Brodersen, S. Andersen, C. Jacobsen, et al., Determination of reserve albumin equivalent for ligand binding, probing two distinct binding functions of the protein, Analytical Biochem. 121: 395 (1982).CrossRefGoogle Scholar
  8. 8.
    W. J. Cashore, W. Oh, W. E. Blumberg, J. Eisinger, and A. A. Lamola, Rapid fluorometric assay of bilirubin and bilirubin binding capacity in blood of jaundiced neonates: comparisons with other methods, Pediatrics 66: 411 (1980).PubMedGoogle Scholar
  9. 9.
    R. Brodersen, Competitive binding of bilirubin and drugs to human serum albumin studied by enzymatic oxidation, J. Clin. Invest. 54:1353 (1974).PubMedCrossRefGoogle Scholar
  10. 10.
    W. J. Cashore, M. Funato, G. Peter, and W. Oh, Displacement of bilirubin from albumin by two Cephalosporins, Ped. Res., 16: 122A (1982) (abstract).Google Scholar
  11. 11.
    S. Øie and G. Levy, Effect of sulfisoxazole on pharmacokinetics of free and plasma protein bound bilirubin in experimental unconjugated hyperbilirubinemia, J. Pharmaceut. Sci., 68:6 (1979).CrossRefGoogle Scholar
  12. 12.
    W. J. Cashore, R. Brodersen, and W. Oh, In vitro and in vivo effects of furosemide on bilirubin binding to albumin, Develop. Pharmacol. and Therapeut. (1983) (in press).Google Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • William J. Cashore
    • 1
    • 2
  • Masahisa Funato
    • 1
    • 2
  1. 1.Department of PediatricsBrown University Program in MedicineProvidenceUSA
  2. 2.Department of PediatricsWomen and Infants Hospital of RIProvidenceUSA

Personalised recommendations