Cancer Chemotherapy and Pharmacology

, Volume 10, Issue 1, pp 40–42 | Cite as

Binding of vinblastine to recrystallized human α1-acid glycoprotein

  • W. H. Steele
  • D. J. Haughton
  • H. E. Barber
Original Articles Vinblastine Acid Glycoprotein Protein Binding

Summary

The binding of vinblastine (VLB) to recrystallized human α1-acid glycoprotein (α1-AGP) dissolved in phosphate-buffered saline (pH 7.4) was determined at different drug concentrations using the technique of continuous ultrafiltration. Vinblastine was extremely highly bound (>99.0%) at a drug concentration of 4.0 μmol·l-1, dropping to under 60% at 65.0 μmol·l-1. Binding was best described by a two-class model with higher-(9.4 μM-1) and lower-(0.1 μM-1) affinity sites but with a similar number of binding sites (1.5 as against 1.1 lower-affinity sites). These results strongly suggest that α1-AGP would be a major binding protein for VLB in plasma.

Keywords

Cancer Research Drug Concentration Vinblastine Major Binding Major Binding Protein 
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.

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References

  1. 1.
    Bang NU, Heidenreich RO, Trygstad CW (1972) Plasma protein requirements for human platelet aggregation. Ann NY Acad Sci 201:280–299Google Scholar
  2. 2.
    BMDP-81 (1981) Biomedical Computer Programs. University of California, Berkeley, USAGoogle Scholar
  3. 3.
    Boxenbaum HG, Riegelman S, Elashoff RM (1974) Statistical estimations in pharmacokinetics. J Pharmacokinet Biopharm 2:123–148Google Scholar
  4. 4.
    Chio L-F. Oon CJ (1979) Changes in serum alpha1 antitrypsin, alpha1 acid glycoprotein and beta2 glycoprotein in patients with malignant hepatocellular carcinoma. Am Cancer Soc 43:596–604Google Scholar
  5. 5.
    De Vita VT, Carrellos GP, Moxley JH (1972) A decade of combination chemotherapy of advanced Hodgkin's disease. Cancer 30:1495–1504Google Scholar
  6. 6.
    Donigian DW, Owellen RJ (1973) Interaction of vinblastine, vincristine and colchicine with serum proteins. Biochem Pharmacol 22:2113–2119Google Scholar
  7. 7.
    Hanser MS, Bang NU (1979) Plasma protein regulation of platelet function and metabolism. Mol Cell Biochem 24:143–158Google Scholar
  8. 8.
    Hebden HF, Radfield JR, Beer CT (1970) The binding of vinblastine by platelets in the rat. Cancer Res 30:1417–1424Google Scholar
  9. 9.
    Horshman S, Reynolds VH, Neumaster T, Patikas P, Worrall T (1974) The prognostic significance of serial serumucoid analysis in patients with cancer. Cancer 34:291–299Google Scholar
  10. 10.
    Kelton JG, McDonald JWD, Barr RM, Walker I, Nicholson W, Neame PB, Hamid C, Wong TY, Hirsh J (1981) Reversible binding of vinblastine to platelets: implications for therapy. Blood 57:431–436Google Scholar
  11. 11.
    Keyser JW (1954) Effect of nitrogen mustard or X-or radium irradiation treatment on the level of blood serum protein-bound carbohydrate (polysaccharide) in patients with neoplastic diseases. Br J Cancer 8:238–250Google Scholar
  12. 12.
    Newton DW, Kluza RB (1978) pKa values of medicinal compounds in pharmacy practice. Drug Intell Clin Pharmacol 12:546–554Google Scholar
  13. 13.
    Nicholson WM, Beard MEJ, Crowther D, Stansfield AG, Malpas JS, Fairley GH, Scott RB (1970) Combination chemotherapy in generalised Hodgkin's disease. Br Medical J 3:7–10Google Scholar
  14. 14.
    Piafsky KM, Borga O (1977) Plasma protein binding of basic drugs. II. Importance of 42-1 glycoprotein for interindividual variation. Clin Pharmacol Ther 22:545–549Google Scholar
  15. 15.
    Roberts J, Keyser JW, Baum M (1975) Serum 42-2 glycoprotein as an index of dissemination in breast cancer. Br J Surg 62:816–819Google Scholar
  16. 16.
    Snyder S, Ashwell G (1971) Quantitation of specific serum glycoproteins in malignancy. Clin Chim Acta 34:449–455Google Scholar
  17. 17.
    Steele WH, Barber HE, Dawson AA, King DJ, Petrie JC (1982a) Protein binding of prednisolone and vinblastine in the serum of normal subjects. Br J Clin Pharmacol 13:595P-596PGoogle Scholar
  18. 18.
    Weiss JF, Morantz RA, Bradley WP, Chretien PB (1979) Serum acute-phase proteins and immunonoglobulins in patients with gliomas. Cancer Res 39:542–544Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • W. H. Steele
    • 1
  • D. J. Haughton
    • 2
  • H. E. Barber
    • 2
  1. 1.Department of Therapeutics & Clinical PharmacologyUniversity Medical BuildingsAberdeenGreat Britain
  2. 2.Department of PharmacologyUniversity Medical BuildingsAberdeenGreat Britain

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