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Pharmacokinetics of ibuprofen in man—III: Plasma protein binding

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Abstract

Plasma protein binding of ibuprofen was measured by equilibrium dialysis on 406 plasma samples collected from 15 normal volunteers following doses of 400, 800, and 1200 mg of ibuprofen as tablets (N=102, 100, 104, respectively) and 420 mg as an aqueous solution (N=100). Individual subject bound concentration at dialysis equilibrium (Cbd) vs. free concentration at dialysis equilibrium (Cfd) were well fitted via computer to the Scatchard equation with one class of binding sites. The binding capacity averaged 1231 μM (range 848–1658 μM), and the association constant averaged 1.76 × 105M−1 (range 1.15 × 105 to 2.73 × 105M−1). Distributional analysis was performed on the free fraction (fd) and bound/free ratios (Cbd/Cfd=1/fd−1) at dialysis equilibrium for each treatment. Using pooled data of all four treatments, distributional analysis was also performed on the free fractions (f) and bound/free ratios (Cb/Cf=1/f−1) corresponding to the plasma drug concentrations in blood as it was withdrawn from the subjects. The bound/free ratios were normally distributed, whereas the distributions of the free fractions were skewed towards higher values.

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References

  1. R. F. N. Mills, S. S. Adams, E. E. Cliffe, W. Dickinson, and J. S. Nicholson. The metabolism of ibuprofen.Xenobiotica 3:589–598 (1973).

    Article  CAS  PubMed  Google Scholar 

  2. J. B. Whitlam, M. J. Crooks, K. F. Brown, and P. V. Pedersen. Binding of nonsteroidal anti-inflammatory agents to proteins—I. Ibuprofen-serum albumin interaction.Biochem. Pharmacol. 28:675–678 (1979).

    Article  CAS  PubMed  Google Scholar 

  3. A. Kober and I. Sjöholm. The binding sites on human serum albumin for some nonsteroidal anti-inflammatory drugs.Mol. Pharmacol. 18:421–426 (1980).

    CAS  PubMed  Google Scholar 

  4. J. B. Whitlam and K. F. Brown. Ultrafiltration in serum protein binding determinations.J. Pharm. Sci. 70:146–150 (1981).

    Article  CAS  PubMed  Google Scholar 

  5. S. Wanwimolruk, D. J. Birkett, and P. M. Brooks. Protein binding of some non-steroidal anti-inflammatory drugs in rheumatoid arthritis.Clin. Pharmacokin. 7:85–92 (1982).

    Article  CAS  Google Scholar 

  6. G. F. Lockwood, K. S. Albert, W. R. Gillespie, G. G. Bole, T. M. Harkcom, G. J. Szpunar, and J. G. Wagner. Pharmacokinetics of ibuprofen in man—I. Free and total area/dose relationships.Clin. Pharmacol. Ther. 34:97–103 (1983).

    Article  CAS  PubMed  Google Scholar 

  7. G. F. Lockwood and J. G. Wagner. High pressure liquid Chromatographic determination of ibuprofen and its major metabolites in biological fluids.J. Chromatogr. 232:335–343 (1982).

    Article  CAS  PubMed  Google Scholar 

  8. T. N. Tozer. Protein binding estimates in the presence of volume shifts during equilibrium dialysis. Presented at the Sidney Riegelman Memorial Symposium: Pharmacokinetics, a Modern View. University of California, San Francisco, April, 1982.

    Google Scholar 

  9. G. F. Lockwood and J. G. Wagner. Plasma volume changes as a result of equilibrium dialysis.J. Pharm. Pharmacol. 35:387–388 (1983).

    Article  CAS  PubMed  Google Scholar 

  10. H. L. Behm and J. G. Wagner. Errors in interpretation of data from equilibrium dialysis protein binding experiments.Res. Commun. Chem. Pathol. Pharmacol. 26:145–160 (1979).

    CAS  PubMed  Google Scholar 

  11. G. Scatchard. The attractions of proteins for small molecules and ions.Ann. N.Y. Acad. Sci. 51:660–672 (1949).

    Article  CAS  Google Scholar 

  12. G. N. Wilkinson. Statistical estimations in enzyme kinetics.Biochem. J. 80:324–332 (1961).

    CAS  PubMed Central  PubMed  Google Scholar 

  13. D. J. Fox and K. E. Guire.MIDAS, The Statistical Research Laboratory. 3rd ed. The University of Michigan, 1976.

  14. H. W. Lilliefors. On the Kolmogorov-Smirnov test for normality with mean and variance unknown.J.A.S.A. 62:399–402 (1967).

    Article  Google Scholar 

  15. D. T. Vowles and B. Marchant. Protein binding of ibuprofen and its relationship to drug interaction.Br. J. Clin. Pract., Suppl. 6, 13–19, (1979).

    Google Scholar 

  16. A. J. Sedman and J. G. Wagner. Quantitative pooling of Michaelis Menten equations in models with parallel metabolite formation paths.J Pharmacokin. Biopharm. 2:149–160 (1974).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. College of Pharmacy and Upjohn Center for Clinical Pharmacology, The University of Michigan, 48109, Ann Arbor, Michigan

    Graham F. Lockwood, Gregory J. Szpunar & John G. Wagner

  2. Department of Biopharmaceutics, The Upjohn Company, 49001, Kalamazoo, Michigan

    Kenneth S. Albert

Authors
  1. Graham F. Lockwood
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  2. Kenneth S. Albert
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  3. Gregory J. Szpunar
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  4. John G. Wagner
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This work was supported by a contract from The Upjohn Company.

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Lockwood, G.F., Albert, K.S., Szpunar, G.J. et al. Pharmacokinetics of ibuprofen in man—III: Plasma protein binding. Journal of Pharmacokinetics and Biopharmaceutics 11, 469–482 (1983). https://doi.org/10.1007/BF01062206

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  • DOI: https://doi.org/10.1007/BF01062206

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