European Journal of Clinical Pharmacology

, Volume 25, Issue 5, pp 703–708 | Cite as

Protein binding of enprofylline

  • K. Tegnér
  • O. Borgå
  • I. Svensson


The protein binding of enprofylline, 3-propylxanthine, in plasma was studied by equilibrium dialysis and ultrafiltration under various experimental conditions. A limited comparison with theophylline was also undertaken. The mean fraction of enprofylline bound in human plasma at 20°C was 47.3±1.1% (SD), which was only 2% less than theophylline. The binding of the two drugs increased dramatically in the pH range 7.2 to 7.8, as reported previously for theophylline. Reasonable agreement was found between equilibrium dialysis and ultrafiltration, but the latter technique proved impractical, because pH control was difficult to achieve. A pronounced species difference in the binding of enprofylline was found. At pH 7.4 an almost constant level of binding of 57% in dog and 81% in rat was found up to 2 · 10−5 M (approx. 4 mg/l). Corresponding values in human and monkey plasma were 47 and 48%, respectively, up to 10−4 M (approx. 20 mg/l).

Key words

enprofylline 3-propylxanthine protein binding equilibrium dialysis theophylline ultrafiltration pH effect species differences 


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  1. Andersen AC (1970) The beagle as an experimental dog. Iowa State University Press, Iowa, p 282Google Scholar
  2. Albary AA, Vallner JJ, Whitworth CW (1981) Binding of xanthine derivatives to human serum albumin as a function of pH. Acta Pharm Suec 18: 379–390Google Scholar
  3. Borgå O, Andersson KE, Edholm LE, Fagerström PO, Lunell E, Persson CGA (1983) Enprofylline kinetics in healthy subjects after single doses. Clin Pharmacol Ther (in press)Google Scholar
  4. Borgå O, Odar-Cederlöf I, Ringberger V-A, Norlin A (1976) Protein binding of salicylate in uremic and normal plasma. Clin Pharmacol Ther 20: 464–475Google Scholar
  5. Brinkschulte M, Breyer-Pfaff U (1979) Binding of tricyclic antidepressants and perazine to human plasma. Naunyn Schmiedeberg's Arch Pharmacol 308: 1–7Google Scholar
  6. Ehrnebo M, Agurell B, Jalling B, Boréus LO (1971) Age differences in drug binding by plasma proteins: Studies on human foetuses, neonates and adults. Eur J Clin Pharmacol 3: 189–193Google Scholar
  7. Franksson G, Änggård E (1970) The plasma protein binding of amphetamine, catecholamines and related compounds. Acta Pharmacol Toxicol 28: 209–214Google Scholar
  8. Gillette JR (1976) Overview of factors affecting drug interactions. Ann NY Acad Sci 281: 136–150Google Scholar
  9. Laursen LC, Johannesson N, Dirksen A, Djurup R, Munch E, Taudorf E, Weeke B (1983) Enprofylline — effects of a new bronchodilating xanthine derivative in asthmatic patients. Allergy 38: 75–79Google Scholar
  10. Laursen LC, Johannesson N, Fagerström PO, Weeke B (1983) Intravenous administration of enprofylline to asthmatic patients. Eur J Clin Pharmacol 24: 323–327Google Scholar
  11. Lunell E, Borgå O, Larsson R (1983) Pharmacokinetics of enprofylline in patients with impaired renal function after intravenous single dose administration. Eur J Clin Pharmacol (in press)Google Scholar
  12. Lunell E, Svedmyr N, Andersson KE, Persson CGA (1982) Effects of enprofylline, a xanthine lacking adenosine receptor antagonism, in patients with chronic obstructive lung disease. Eur J Clin Pharmacol 22: 395–402Google Scholar
  13. Persson CGA, Erjefält I (1982) Seizure activity in animals given enprofylline and theophylline, two xanthines with partly different mechanisms of action. Arch Int Pharmacodyn Ther 258: 267–282Google Scholar
  14. Persson CGA, Erjefält I, Edholm LE, Karlsson JA, Lamm CJ (1982) Tracheal relaxant and cardiostimulant actions of xanthines can be differentiated from diuretic and CNS-stimulant effects. Role of adenosine antagonism? Life Sci 30: 2673–2681Google Scholar
  15. Persson CGA, Erjefält I, Karlsson JA (1981) Adenosine antagonism, a less desirable characteristic of xanthine asthma drugs? Acta Pharmacol Toxicol 49: 317–320Google Scholar
  16. Persson CGA, Karlsson JA, Erjefält I (1982) Differentiation between bronchodilation and universal adenosine antagonism among xanthine derivatives. Life Sci 30: 2181–2189Google Scholar
  17. Persson CGA, Kjellin G (1981) Enprofylline, a principally new antiasthmatic xanthine. Acta Pharmacol Toxicol 49: 313–316Google Scholar
  18. Piafsky KM, Sitar DS, Rangno RE, Ogilvie RJ (1977) Theophylline kinetics in acute pulmonary edema. Clin Pharmacol Ther 21: 310–316Google Scholar
  19. Rauen HM (1964) Biochemisches Taschenbuch II, Springer, Berlin Heidelberg New York, p 348Google Scholar
  20. Reidenberg MM (1976) The binding of drugs to plasma proteins from patients with poor renal function. Clin Pharmacokinet 1: 121–125Google Scholar
  21. Scatchard G (1949) The attraction of proteins for small molecules and ions. Ann NY Acad Sci 51: 660–672Google Scholar
  22. Sjöqvist F, Borgå O, L'E Orme M (1980) In: Avery GS (ed) Drug treatment. Principles and practice of clinical pharmacology and therapeutics. 2nd edn. Adis Press, Sydney, pp 1–61Google Scholar
  23. Vallner JJ, Speir WA, Kolbeck RC, Harrison GN, Bransome ED Jr (1979) Effect of pH on the binding of theophylline to serum proteins. Am Rev Respir Dis 120: 83–86Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • K. Tegnér
    • 1
  • O. Borgå
    • 1
  • I. Svensson
    • 1
  1. 1.AB Draco, Pharmacokinetic Laboratory, Research and Development LaboratoriesLundSweden

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