European Journal of Clinical Pharmacology

, Volume 24, Issue 5, pp 683–687 | Cite as

The protein binding of vinblastine in the serum of normal subjects and patients with Hodgkin's disease

  • W. H. Steele
  • D. J. King
  • H. E. Barber
  • G. M. Hawksworth
  • A. A. Dawson
  • J. C. Petrie


The protein binding of vinblastine was measured in the serum from 6 normal subjects and 9 patients with Hodgkin's disease. Cellulose acetate electrophoresis showed that the predominant binding protein fractions were the α1- and α2-globulins with little binding to albumin and β- and γ-globulins. At a serum concentration of 10 nM a significantly lower percentage bound was found in the patient group (p=0.001). Binding to both groups was very high at 99.7% bound in the normal subjects and 98.9% bound in the patient group. Binding in both groups was best described by a two class protein binding model with higher and lower affinity binding sites. No significant difference was found on inter-group comparisons of binding parameter values.

Key words

vinblastine protein binding Hodgkin's disease 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ahn YS, Byrnes JJ, Harrington WJ, Cayer ML, Smith DS, Burnskill DE, Pall LM (1978) The treatment of idiopathic thrombocytopenia with vinblastine-loaded platelets. N Engl J Med 298: 1101–1104Google Scholar
  2. 2.
    BMDP-81, Biomedical Computer Programs, University of California (1981)Google 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-acid glycoprotein and beta2-glycoprotein in patients with malignant hepatocellular carcinoma. Am Cancer Soc 43: 596–604Google Scholar
  5. 5.
    De Vita VT, Canellos 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.
    Gibaldi M, McNamara PJ (1978) Apparent volume of distribution and drug binding to plasma proteins and tissues. Eur J Clin Pharmacol 13: 373–378Google Scholar
  8. 8.
    Hebden HF, Hadfield JR, Beer CT (1970) The binding of vinblastine by platelets in the rat. Cancer Res 30: 1417–1424Google Scholar
  9. 9.
    Kelton JG, McDonald JWD, Barr RM, Walker I, Nicholson W, Neame PB, Hamid C, Wang TY, Hirsh J (1981) The reversible binding of vinblastine to platelets: Implications for therapy. Blood 57: 431–436Google Scholar
  10. 10.
    Midler GB, Alling EL, Morton IJ (1950) Effect of neoplastic and allied diseases on concentration of plasma proteins Cancer 3: 56–65Google Scholar
  11. 11.
    Nicholson WM, Beard MEJ, Crowther D, Stansfeld AG, Vartan CP, Malpas JS, Fairley GH, Scott RB (1970) Combination chemotherapy in generalized Hodgkin's disease. Br Med J 3: 7–10Google Scholar
  12. 12.
    Owellen RJ, Hartke CA, Hains FO (1977) Pharmacokinetics and metabolism of vinblastine in humans. Cancer Res 37: 2597–2602Google Scholar
  13. 13.
    Piafsky KM, Borga O (1977) Plasma protein binding of basic drugs II. Importance of α1-acid glycoprotein for interindividual variation. Clin Pharmacol Ther 22: 545–549Google Scholar
  14. 14.
    Roberts J, Keyser JW, Baun M (1975) Serum α1-acid glycoprotein as an index of dissemination in breast cancer. Br J Surg 62: 816–819Google Scholar
  15. 15.
    Rosenthal HE (1967) A graphic method for the determination and representation of binding parameters in a complex system. Ann Biochem 20: 525–532Google Scholar
  16. 16.
    Schoeman DW, Azarnoff DL (1975) Diphenylhydantoin potency and plasma protein binding. J Pharmacol Exp Ther 195: 84–86Google Scholar
  17. 17.
    Sethi VS, Burton SS, Jackson DV (1980) A sensitive radioimmunoassay for vincristine and vinblastine. Cancer Chemother Pharmacol 4: 183–187Google Scholar
  18. 18.
    Steele WH, Haughton DJ, Barber HE (1982) Binding of vinblastine to human α1-acid glycoprotein. Cancer Chemother Pharmacol 10: 40–42Google Scholar
  19. 19.
    Steinfeld JL (1960) 131I-Albumin degradation in patients with neoplastic disease. Cancer 13: 974–984Google Scholar
  20. 20.
    Teale JD, Clough JM, Marks V (1977) Radioimmunoassay of vinblastine and vincristine. Br J Clin Pharmacol 4: 169–172Google Scholar
  21. 21.
    Van Os GAJ (1964) In: Ariens EJ (ed) Molecular pharmacology 1. Academic Press, New York, p 20Google Scholar
  22. 22.
    Wagner TG (1976) Simple model to explain effects of plasma protein binding and tissue binding on calculated volumes of distribution, apparent elimination rate constants and clearances. Eur J Clin Pharmacol 10: 425–432Google Scholar
  23. 23.
    Wiess JF, Morantz RA, Bradely WO, Chretien PB (1979) Serum acute-phase proteins and immunoglobulins in patients with gliomas. Cancer Res 39: 542–544Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • W. H. Steele
    • 1
  • D. J. King
    • 2
  • H. E. Barber
    • 1
  • G. M. Hawksworth
    • 1
  • A. A. Dawson
    • 2
  • J. C. Petrie
    • 1
  1. 1.Departments of Clinical Pharmacology and Therapeutics, and PharmacologyUniversity Medical BuildingsForesterhillScotland
  2. 2.Department of MedicineAberdeen Royal InfirmaryForesterhillScotland

Personalised recommendations