European Journal of Clinical Pharmacology

, Volume 21, Issue 5, pp 427–431 | Cite as

Binding of aprindine and moxaprindine to human serum, α1-acid glycoprotein and serum of healthy and diseased humans

  • O. Teirlynck
  • F. M. Belpaire
  • F. Andreasen
Originals

Summary

A comparison was made between the binding of the anti-arrhythmic agents aprindine and moxaprindine to human serum, to human serum albumin (HSA), to α1-acid glycoprotein (α1-AGP) and to a mixture of HSA and α1-AGP. In serum from healthy volunteers (n=4) the binding of aprindine-HCl 5 µg/ml (13.8 µM) was 93.8% (SD±1.0), and that of moxaprindine-HCl 5 µg/ml (12.8 µM) was 94.1% (SD±1.1). Their binding to the mixture of α1-AGP and albumin approximated their binding to serum. For α1-AGP, the binding was similar for both compounds, whereas for HSA the binding of aprindine was more pronounced than that of moxaprindine: for both products the affinity coefficient for binding to α1-AGP was about 100 times greater than that for binding to albumin. In serum from rheumatoid patients and from patients with renal failure a small but significant increase in binding of aprindine and moxaprindine was observed, approximately 1%. Increased and decreased binding was seen in serum from cirrhotic patients; for example, for aprindine the range in cirrhosis was 96.7%–79.8%, and the range in controls was 95.0%–92.4%. Free drug fraction and α1-AGP concentration were inversely correlated. The results show that α1-AGP plays an important role in the binding of aprindine and moxaprindine, and that alteration in the binding of the two compounds in disease states to a large extent can be explained by changes in serum α1-AGP concentration.

Key words

aprindine moxaprindine cirrhosis rheumatoid arthritis uraemia protein binding serum protein alpha1-acid glycoprotein 

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References

  1. 1.
    Piafsky KM, Borgä O (1977) Plasma protein binding of basic drugs. II. Importance of α1-acid glycoprotein for interindividual variation. Clin Pharmacol Ther 22: 545–549Google Scholar
  2. 2.
    Borgä O, Piafsky KM, Nilsen OG (1977) Plasma protein binding of basic drugs. I. Selective displacement from α1-acid glycoprotein by tris (2-butoxyethyl) phosphate. Clin Pharmacol Ther 22: 539–544Google Scholar
  3. 3.
    Piafsky KM, Borgä O, Odar-Cederlöf I, Johansson C, Sjöqvist F (1978) Increased plasma protein binding of propranolol and chlorpromazine mediated by disease-induced elevations of plasma α1-acid glycoprotein. N Engl J Med 299: 1435–1439Google Scholar
  4. 4.
    Schneider RE, Bishop H, Hawkins CF, Kitis G (1979) Drug binding to α1-glycoprotein. Lancet 1: 554Google Scholar
  5. 5.
    Scott BJ, Bradwell AR, Schneider RE, Bishop H (1979) Propranolol binding to serum orosomucoid. Lancet 1: 930Google Scholar
  6. 6.
    Glasson S, Zini R, D'Athis P, Tillement JP, Boissier JR (1980) The distribution of bound propranolol between the different human serum proteins. Mol Pharmacol 17: 187–191Google Scholar
  7. 7.
    Brinkschulte M, Breyer-Pfaff U (1980) The contribution of α1-acid glycoprotein, lipoproteins, and albumin to the plasma binding of perazine, amitriptyline, and nortriptyline in healthy man. Naunyn Schmiedeberg's Arch Pharmacol 314: 61–66Google Scholar
  8. 8.
    Belpaire FM, Bogaert MG, Rosseneu M, Teirlynck O (1981) Binding of β-adrenoceptor antagonists to human serum albumin, α1-acid glycoprotein and human serum. Br J Clin Pharmacol 11:125PGoogle Scholar
  9. 9.
    Andreasen F, Husted S, Jakobsen P, Jensen EB (1980) The binding of aprindine to serum proteins with statistical considerations concerning the analysis of binding data. Acta Pharmacol Toxicol 46: 105–112Google Scholar
  10. 10.
    de Suray JM, Lavis A, Breekpot F (1981) Pharmacokinetic study of aprindine and moxaprindine in dogs. Int J Clin Pharmacol Ther Toxicol 19: 209–215Google Scholar
  11. 11.
    Rosenthal ME (1967) A graphic method for the determination and presentation of binding parameters in a complex system. Anal Biochem 20: 525–532Google Scholar
  12. 12.
    Chio LF, Oon CJ (1979) Changes in serum alpha1 antitrypsin, alpha1 acid glycoprotein and beta2 glycoprotein in patients with malignant hepatocellular carcinoma. Cancer 43: 596–604Google Scholar
  13. 13.
    Van Durme JP, Bogaert MG, Rosseel MT (1974) Therapeutic effectiveness and plasma levels of aprindine, a new antidysrhythmic drug. Eur J Clin Pharmacol 7: 343–345Google Scholar
  14. 14.
    Waleffe A, Guillaume D, Mary-Rabine L, Kulbertus H (1980) The efficacy of intravenous moxaprindine on ventricular ectopic activity. Acta Cardiol 35: 257–268Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • O. Teirlynck
    • 1
  • F. M. Belpaire
    • 1
  • F. Andreasen
    • 2
  1. 1.Heymans Institute of PharmacologyUniversity of Gent Medical SchoolGentBelgium
  2. 2.Division of Clinical Pharmacology, Institute of PharmacologyUniversity of AarhusAarhusDenmark

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