European Journal of Clinical Pharmacology

, Volume 22, Issue 5, pp 417–422 | Cite as

Pharmacokinetics of theophylline in patients following short-term intravenous infusion

  • V. W. Steinijans
  • R. Eicke
  • J. Ahrens
Originals

Summary

Serum theophylline concentrations after intravenous administration of a new short-term infusion (Euphyllin® Kurzzeitinfusion) were measured in 50 out-patients with chronic obstructive airways disease (COAD). An intravenous infusion of theophylline ethylenediamine 480 mg (corresponding to approximately 350 mg anhydrous theophylline) in 50 ml isotonic solution was given in 20 min. Blood samples were taken beforehand and 25 to 30 min and 1, 3 and 6 h after starting the infusion. 86% of the patients had a one-hour serum level in the therapeutic range of 8–20 mg/l, and 2 h later, this was true of 64% of the patients. The short-term infusion was well tolerated, even in cases with unknown high pre-infusion serum levels. Pertinent pharmacokinetic parameters were determined, such as total body clearance, apparent volume of distribution, and half-life of elimination. Geometric mean and 95%-confidence limits, derived from the log-normal distribution of these parameters, were: Cl=0.044 (0.018–0.109) l/h/kg ideal body weight, Vd=0.451 (0.258–0.789) l/kg ideal body weight, and t1/2(el)=7.1 (2.6–19.1) h.

Key words

theophylline aminophylline obstructive airways disease short-term i.v. infusion log-normal distribution pharmacokinetics serum concentrations 

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References

  1. Aubier M, de Troyer A, Sampson M, Macklem PT, Roussos C (1981) Aminophylline improves diaphragmatic contractility. N Engl J Med 305: 249–252Google Scholar
  2. Boysen PG, Robinson JD, de Marco FJ, Krischer JP (1979) Pharmacokinctics of theophylline: A two-compartment instructional model. Anaesthesiology 51: 337Google Scholar
  3. Chrzanowski FA, Niebergall PJ, Mayock RL, Taubin JM, Sugita ET (1977) Kinetics of intravenous theophylline. Clin Pharmacol Ther 22: 188–195Google Scholar
  4. Eatman FB, Colburn WA, Boxenbaum HG, Posmanter HN, Weinfeld RE, Ronfeld R, Weissman L, Moore JD, Gibaldi M, Kaplan SA (1977) Pharmacokinetics of diazepam following multiple-dose oral administration to healthy human subjects. J Pharmacokinet Biopharm 5: 481–494Google Scholar
  5. Fabel H, Wettengel M (1968) Einfluß von Aminophyllin auf das Ventilations-Perfusions-Verhältnis bei obstruktiven Ventilationsstörungen. Beitr Klin Erforsch Tuberk Lungenkr 141: 164–169Google Scholar
  6. Greger G, Ahrens J (1981) Therapie der Atemwegsobstruktion mit einer neuartigen Theophyllin-Kurzzeitinfusion. Klinikarzt 10: 550–556Google Scholar
  7. Ghory AC, Patterson R (1980) Treating asthma in the elderly. Geriatrics 35: 32–38Google Scholar
  8. Hendeles L, Weinberger M, Bighley L (1978) Disposition of theophylline after a single intravenous infusion of aminophylline. Am Rev Respir Dis 118: 97–103Google Scholar
  9. Hermann G, Aynesworth MB (1937) Successful treatment of persistent extreme dispnoe ‘status asthmaticus’. Use of theophylline ethylenediamine (aminophylline). J Lab Clin Med 23: 135–143Google Scholar
  10. Jusko WJ, Gardner MJ, Mangione A, Schentag JJ, Koup JR, Vance JW (1979) Factors affecting theophylline clearances: Age, tobacco, marijuana, cirrhosis, congestive heart failure, obesity, oral contraceptives, bezodiazepines, barbiturates, and ethanol. J Pharm Sci 68: 1358–1365Google Scholar
  11. Kolbeck RC, Speir jr. WA, Carrier GO, Bransome jr. ED (1979) Apparent irrelevance of cyclic nucleotides to the relaxation of tracheal smooth muscle induces by theophylline. Lung 156: 173–183Google Scholar
  12. Loo JCK, Riegelman S (1970) Assessment of pharmacokinetic constants from postinfusion blood curves obtained after i.v. infusion. J Pharm Sci 59: 53–55Google Scholar
  13. Magnussen H, Holle JP, Hartmann V, Ahrens J (1980) Der Einfluß von intravenös appliziertem Euphyllin auf die Atemmechanik und den Gasaustausch beim Asthma bronchiale. In: Wettengel R (ed) Asthma-Therapie mit Theophyllin. Optimierung durch Blutspiegel-Bestimmung. Dustri, München-DeisenhofenGoogle Scholar
  14. Matthys H, Köhler D (1980) Effect of theophylline on mucociliary clearance in man. Eur J Respir Dis (Suppl) 61: 98–102Google Scholar
  15. Metzler CM (1974) Bioavailability — a problem in equivalence. Biometrics 30: 309–317Google Scholar
  16. Mitenko PA, Ogilvie RI (1973) Pharmacokinetics of intravenous theophylline. Clin Pharmacol Ther 14: 509–513Google Scholar
  17. Nolte D (1980) Asthma. Das Krankheitsbild — Der Asthmapatient — Die Therapie. Urban & Schwarzenberg, München Wien BaltimoreGoogle Scholar
  18. Ogilvie RI (1978) Clinical Pharmacokinetics of theophylline. Clin Pharmacokinet 3: 267–293Google Scholar
  19. Owen DB (1962) Handbook of statistical tables. Addison-Wesley, Reading, MAGoogle Scholar
  20. Pancorbo S, Sawchuk RJ, Dashe CH, Schallock M (1979) Use of a pharmacokinetic model for individualizing intravenous doses of aminophylline. Eur J Clin Pharmacol 16: 251–254Google Scholar
  21. Pearson ES, Hartley HO (1966) Biometrika tables for statisticians, Vol I, 3rd edition. Cambridge University Press, CambridgeGoogle Scholar
  22. Powell JR, Vozeh S, Hopewell P, Costello J, Sheiner LB, Riegelman S (1978) Theophylline disposition in acutely ill hospitalized patients. Am Rev Respir Dis 118: 229–238Google Scholar
  23. Riegelman S, Loo J, Rowland M (1968) Concept of a volume of distribution and possible errors in evaluation of this parameter. J Pharm Sci 57: 128–133Google Scholar
  24. Riegelman S, Sheiner LB, Beal SL (1980) Population based approach to pharmacokinetics and bioavailability studies in patients. In: Gladtke E, Heimann G (eds) Pharmacokinetics. Gustav Fischer, Stuttgart New YorkGoogle Scholar
  25. Rossing TH, Fanta CH, Goldstein DH, Snapper JR, McFadden jr. ER (1980) Emergency therapy of asthma: Comparison of the acute effects of parenteral and inhaled sympathomimetics and infused aminophylline. Am Rev Respir Dis 122: 365–371Google Scholar
  26. Sugihara H (1979) Basal pathomechanism of asthmatic attacks (A Review). Ann Allergy 42: 99–108Google Scholar
  27. Svedmyr K, Mellstrand T, Svedmyr N (1977) Comparison between effects of aminophylline, proxyphylline and terbutaline in asthmatics. Acta Pharmacol Toxicol 41: 77Google Scholar
  28. Vozeh S, Kewitz G, Wenk M, Follath F (1980) Rapid prediction of steady-state serum theophylline concentration in patients treated with intravenous aminophylline. Eur J Clin Pharmacol 18: 473–477Google Scholar
  29. Westlake WJ (1973) Use of statistical methods in evaluation of in vivo performance of dosage forms. J Pharm Sci 62: 1579–1589Google Scholar
  30. Zwillich CW, Sutton FD, Neff TA, Cohn WM, Watthay RA, Weinberger M (1975) Theophylline-induced seizures in adults. Correlation with serum concentrations. Ann Intern Med 82: 784–787Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • V. W. Steinijans
    • 1
  • R. Eicke
    • 2
  • J. Ahrens
    • 3
  1. 1.Biometry DepartmentByk Gulden Research CentreKonstanzFederal Republic of Germany
  2. 2.PulmonologistWuppertalFederal Republic of Germany
  3. 3.Medical Science DepartmentByk Gulden PharmaceuticalsKonstanzFederal Republic of Germany

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