Pharmaceutisch Weekblad

, Volume 8, Issue 1, pp 42–45 | Cite as

The effect of the 4-quinolone enoxacin on plasma theophylline concentrations

  • W. J. A. Wijnands
  • T. B. Vree
  • C. L. A. Van Herwaarden
Quinolones in Perspective


In patients treated concomitantly with theophylline and enoxacin, a broad spectrum antibacterial agent for oral administration, unexpectedly high plasma theophylline concentrations were observed. In six patients receiving intravenous aminophylline under controlled conditions, enoxacin was started in a daily dose of 800 or 1200 mg. Plasma theophylline concentrations increased from 8.4 ± 2.4 mg/l to 15.0 ± 5.1 mg/l at day 3 of co-administration. Total body clearance of theophylline decreased significantly, whereas renal clearance and protein binding did not change. When enoxacin, 800 mg daily, was administered to seven patients with a stable chronic obstructive pulmonary disease, who were on long-term theophylline treatment a significant increase in plasma theophylline concentrations occurred as well: elimination half-life was prolonged. It is concluded that the rise of plasma theophylline concentrations is caused by a reduced metabolic clearance of theophylline. If concomitant use of both drugs is necessary, monitoring of plasma theophylline concentration and adjustment of the theophylline dose is recommended, to avoid toxicity.

Key words

Drug interactions Enoxacin Lung disease, obstructive Metabolic clearance Theophylline 


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  1. 1.
    Mitenko PA, Ogilvie RI. Rational intravenous doses of theophylline. N Engl J Med 1973;289:600–3.Google Scholar
  2. 2.
    Ellis EF, Koysooko R, Levy G. Pharmacokinetics of theophylline in children with asthma. Pediatrics 1976;58:542–7.Google Scholar
  3. 3.
    Jusko WJ. Role of tobacco smoking in pharmacokinetics. J Pharmacokinet Biopharm 1978;6:7.Google Scholar
  4. 4.
    Feldman CH, Hutchinson VE, Pippenger CE, Blumenfeld TA, Feldman BR, Davis WJ. Effect of dietary protein and carbohydrate on theophylline metabolism in children. Pediatrics 1980;166:956–62.Google Scholar
  5. 5.
    Landay RA, Gonzales MA, Taylor JC. Effect of phenobarbital on theophylline disposition. J Allergy Clin Immunol 1978;62:27–9.Google Scholar
  6. 6.
    Marquis JF, Carruthers SG, Spence JD, Brownstone YS, Toogood JH. Phenytoin-theophylline interaction. N Engl J Med 1982;307:1189–90.Google Scholar
  7. 7.
    Hemsted MP, Miles MV, Rutland RO. Effect of intravenous isoproterenol on theophylline kinetics. J Allergy Clin Immunol 1982;69:360–4.Google Scholar
  8. 8.
    Zwillich CW, Sutton FD, Neff TA, Cohn WM, Matthay RA, Weinberger MM. Theophylline-induced seizures in adults. Ann Intern Med 1975;82:784–7.Google Scholar
  9. 9.
    Clark CJ, Boyd G. Theophylline pharmacokinetics during respiratory viral infection. Lancet 1979;1:492.Google Scholar
  10. 10.
    Mangione A, Imhoff TE, Lee RV, Shum LY, Jusko WJ. Pharmacokinetics of theophylline in hepatic disease. Chest 1978;73:616–22.Google Scholar
  11. 11.
    Manfredi RL, Vesell ES. Inhibition of theophylline metabolism by long-term allopurinol administration. Clin Pharmacol Ther 1981;129:224–9.Google Scholar
  12. 12.
    Jackson JE, Powell JR, Wandell M, Bentley J, Dorr R. Cimetidine decreases theophylline clearance. Am Rev Resp Dis 1981;123:615–7.Google Scholar
  13. 13.
    Prince RA, Wing DS, Weinberger MM, Hendeles LS, Riegelman S. Effect of erythromycin on theophylline kinetics. J Allergy Clin Immunol 1981;68:427–31.Google Scholar
  14. 14.
    Weinberger M, Hudgel D, Spector S, Chidsey C. Inhibition of theophylline clearance by troleandomycin. J Allergy Clin Immunol 1977;59:228–31.Google Scholar
  15. 15.
    Conrad KA, Nyman DW. Effects of metoprolol and propranolol on theophylline elimination. Clin Pharmacol Ther 1980;28:463–7.Google Scholar
  16. 16.
    Wijnands WJ, Van Herwaarden CL, Vree TB. Enoxacin raises plasma theophylline concentrations. Lancet 1984;2:108–9.Google Scholar
  17. 17.
    Hendeles L, Weinberger M. Theophylline: A ‘state of art’ review. Pharmacotherapy 1983;3:2–44.Google Scholar
  18. 18.
    Jonkman J, Upton R. Pharmacokinetic drug interactions with theophylline. Clin Pharmacokinet 1984;9:309–34.Google Scholar
  19. 19.
    Gushaw JB, Hu MW, Singh P, Miller JG, Schneider RS. Homogenous enzyme immunoassay for theophylline in serum. Clin Chem 1977;23:1144.Google Scholar
  20. 20.
    Koup JR, Brodsky B. Comparison of homogenous enzyme immunoassay and high pressure liquid chromatography for the determination of theophylline concentrations in serum. Am Rev Resp Dis 1978;117:35–8.Google Scholar
  21. 21.
    Davies BI, Maessen FP, Teengs JP. Serum and sputum concentrations of enoxacin after oral single dosing in a clinical and bacteriological study. J Antimicrob Chempther 1984;14(suppl C):83–9.Google Scholar
  22. 22.
    Lohmann SM, Miech RP. Theophylline metabolism by the rat liver microsomal system. J Pharmacol Exp Ther 1976;196:213–25.Google Scholar
  23. 23.
    Grygiel JJ, Miners JO, Drew R, Birkett DJ. Differential effects of cimetidine on theophylline metabolic pathways. Eur J Clin Pharmacol 1984;26:335–40.Google Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1986

Authors and Affiliations

  • W. J. A. Wijnands
    • 1
  • T. B. Vree
    • 2
  • C. L. A. Van Herwaarden
    • 1
  1. 1.Department of Pulmonary DiseaseMedical Centre DekkerswaldCA Heilige LandstichtingThe Netherlands
  2. 2.Department of Clinical Pharmacy, St. Radboud HospitalCatholic University of NijmegenHB NijmegenThe Netherlands

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