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. 1990 Jun;34(6):1249–1253. doi: 10.1128/aac.34.6.1249

Safety of fleroxacin coadministered with theophylline to young and elderly volunteers.

M Parent 1, M St-Laurent 1, M LeBel 1
PMCID: PMC171793  PMID: 2118328

Abstract

The influence of multiple doses of fleroxacin on the plasma clearance and the urinary excretion of theophylline was studied in 19 young and 18 elderly male volunteers. A theophylline dosage individualized to obtain a mean theophylline concentration in plasma of 10 +/- 3 micrograms/ml was administered for 1 week to each subject. At week 2, oral fleroxacin (400 mg once daily) was added. Theophylline concentrations in plasma were measured with TDx (Abbott Diagnostics, Mississauga, Ontario, Canada), and urinary excretion of theophylline and its three major metabolites was measured by high-performance liquid chromatography. Total theophylline clearance remained essentially unchanged throughout the study period (3.5 and 2.9 liters/h in the young and the elderly, respectively) both after a single fleroxacin dose and after multiple doses. Although significant changes occurred in the urinary excretion of unchanged theophylline and its metabolites after a single fleroxacin dose, no changes were observed after multiple doses. Side effects consisted mainly of gastrointestinal and sleep disturbances, more related to theophylline; photosensitivity was observed in six subjects and was attributed to fleroxacin. We conclude that fleroxacin may be administered concomitantly with theophylline in either young or elderly patients. Close monitoring of theophylline concentrations in serum should be performed, particularly in patients with chronic obstructive pulmonary disease, for whom data are currently lacking.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beckmann J., Elsässer W., Gundert-Remy U., Hertrampf R. Enoxacin--a potent inhibitor of theophylline metabolism. Eur J Clin Pharmacol. 1987;33(3):227–230. doi: 10.1007/BF00637553. [DOI] [PubMed] [Google Scholar]
  2. Bowie W. R., Willetts V., Jewesson P. J. Adverse reactions in a dose-ranging study with a new long-acting fluoroquinolone, fleroxacin. Antimicrob Agents Chemother. 1989 Oct;33(10):1778–1782. doi: 10.1128/aac.33.10.1778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bowles S. K., Popovski Z., Rybak M. J., Beckman H. B., Edwards D. J. Effect of norfloxacin on theophylline pharmacokinetics at steady state. Antimicrob Agents Chemother. 1988 Apr;32(4):510–512. doi: 10.1128/aac.32.4.510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Davis R. L., Kelly H. W., Quenzer R. W., Standefer J., Steinberg B., Gallegos J. Effect of norfloxacin on theophylline metabolism. Antimicrob Agents Chemother. 1989 Feb;33(2):212–214. doi: 10.1128/aac.33.2.212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Edwards D. J., Waite N. M., Svensson C. K. Effect of enoxacin and 4-oxo-enoxacin on antipyrine disposition in the rat. Drug Metab Dispos. 1988 Jul-Aug;16(4):653–655. [PubMed] [Google Scholar]
  6. Fourtillan J. B., Granier J., Saint-Salvi B., Salmon J., Surjus A., Tremblay D., Vincent Du Laurier M., Beck S. Pharmacokinetics of ofloxacin and theophylline alone and in combination. Infection. 1986;14 (Suppl 1):S67–S69. doi: 10.1007/BF01645203. [DOI] [PubMed] [Google Scholar]
  7. Grech-Bélanger O., Francoeur J., Le Bel M. The effect of fleroxacin on hepatic drug metabolism in the rat. Res Commun Chem Pathol Pharmacol. 1989 Apr;64(1):121–133. [PubMed] [Google Scholar]
  8. Gregoire S. L., Grasela T. H., Jr, Freer J. P., Tack K. J., Schentag J. J. Inhibition of theophylline clearance by coadministered ofloxacin without alteration of theophylline effects. Antimicrob Agents Chemother. 1987 Mar;31(3):375–378. doi: 10.1128/aac.31.3.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Healy D. P., Polk R. E., Kanawati L., Rock D. T., Mooney M. L. Interaction between oral ciprofloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother. 1989 Apr;33(4):474–478. doi: 10.1128/aac.33.4.474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ho G., Tierney M. G., Dales R. E. Evaluation of the effect of norfloxacin on the pharmacokinetics of theophylline. Clin Pharmacol Ther. 1988 Jul;44(1):35–38. doi: 10.1038/clpt.1988.109. [DOI] [PubMed] [Google Scholar]
  11. Horai Y., Ishizaki T., Sasaki T., Watanabe M., Kabe J. Individualized aminophylline therapy in patients with obstructive airway disease: oral dosage prediction from an intravenous test dose. Eur J Clin Pharmacol. 1982;23(2):111–121. doi: 10.1007/BF00545964. [DOI] [PubMed] [Google Scholar]
  12. Kester M. B., Saccar C. L., Rocci M. L., Jr, Mansmann H. C., Jr New simplified microassay for the quantitation of theophylline and its major metabolites in serum by high-performance liquid chromatography. J Chromatogr. 1986 Jul 11;380(1):99–108. doi: 10.1016/s0378-4347(00)83628-2. [DOI] [PubMed] [Google Scholar]
  13. Lalonde R. L., Bottorff M. B., Straughn A. B. Comparison of high pressure liquid chromatography and fluorescence polarization immunoassay methods in a theophylline pharmacokinetic study. Ther Drug Monit. 1985;7(4):442–446. doi: 10.1097/00007691-198512000-00014. [DOI] [PubMed] [Google Scholar]
  14. LeBel M., Vallée F., St-Laurent M. Influence of lomefloxacin on the pharmacokinetics of theophylline. Antimicrob Agents Chemother. 1990 Jun;34(6):1254–1256. doi: 10.1128/aac.34.6.1254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Maesen F. P., Teengs J. P., Baur C., Davies B. I. Quinolones and raised plasma concentrations of theophylline. Lancet. 1984 Sep 1;2(8401):530–530. doi: 10.1016/s0140-6736(84)92617-5. [DOI] [PubMed] [Google Scholar]
  16. Niki Y., Soejima R., Kawane H., Sumi M., Umeki S. New synthetic quinolone antibacterial agents and serum concentration of theophylline. Chest. 1987 Oct;92(4):663–669. doi: 10.1378/chest.92.4.663. [DOI] [PubMed] [Google Scholar]
  17. Nix D. E., DeVito J. M., Whitbread M. A., Schentag J. J. Effect of multiple dose oral ciprofloxacin on the pharmacokinetics of theophylline and indocyanine green. J Antimicrob Chemother. 1987 Feb;19(2):263–269. doi: 10.1093/jac/19.2.263. [DOI] [PubMed] [Google Scholar]
  18. Nix D. E., Norman A., Schentag J. J. Effect of lomefloxacin on theophylline pharmacokinetics. Antimicrob Agents Chemother. 1989 Jul;33(7):1006–1008. doi: 10.1128/aac.33.7.1006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Oeltgen P. R., Shank W. A., Jr, Blouin R. A., Clark T. Clinical evaluation of the Abbott TDx fluorescence polarization immunoassay analyzer. Ther Drug Monit. 1984;6(3):360–367. doi: 10.1097/00007691-198409000-00018. [DOI] [PubMed] [Google Scholar]
  20. Panneton A. C., Bergeron M. G., LeBel M. Pharmacokinetics and tissue penetration of fleroxacin after single and multiple 400- and 800-mg-dosage regimens. Antimicrob Agents Chemother. 1988 Oct;32(10):1515–1520. doi: 10.1128/aac.32.10.1515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Raoof S., Wollschlager C., Khan F. A. Ciprofloxacin increases serum levels of theophylline. Am J Med. 1987 Apr 27;82(4A):115–118. [PubMed] [Google Scholar]
  22. Rogge M. C., Solomon W. R., Sedman A. J., Welling P. G., Koup J. R., Wagner J. G. The theophylline-enoxacin interaction: II. Changes in the disposition of theophylline and its metabolites during intermittent administration of enoxacin. Clin Pharmacol Ther. 1989 Oct;46(4):420–428. doi: 10.1038/clpt.1989.160. [DOI] [PubMed] [Google Scholar]
  23. Rogge M. C., Solomon W. R., Sedman A. J., Welling P. G., Toothaker R. D., Wagner J. G. The theophylline-enoxacin interaction: I. Effect of enoxacin dose size on theophylline disposition. Clin Pharmacol Ther. 1988 Nov;44(5):579–587. doi: 10.1038/clpt.1988.197. [DOI] [PubMed] [Google Scholar]
  24. Ross C. A., Kraft C. J., Lee M. H., Haughey D. B. Evaluation of a mouse monoclonal antibody for the determination of serum theophylline by fluorescence polarization immunoassay. Ther Drug Monit. 1985;7(3):355–357. doi: 10.1097/00007691-198507030-00022. [DOI] [PubMed] [Google Scholar]
  25. Rybak M. J., Bowles S. K., Chandrasekar P. H., Edwards D. J. Increased theophylline concentrations secondary to ciprofloxacin. Drug Intell Clin Pharm. 1987 Nov;21(11):879–881. doi: 10.1177/106002808702101106. [DOI] [PubMed] [Google Scholar]
  26. Sano M., Kawakatsu K., Ohkita C., Yamamoto I., Takeyama M., Yamashina H., Goto M. Effects of enoxacin, ofloxacin and norfloxacin on theophylline disposition in humans. Eur J Clin Pharmacol. 1988;35(2):161–165. doi: 10.1007/BF00609246. [DOI] [PubMed] [Google Scholar]
  27. Shin S. G., Juan D., Rammohan M. Theophylline pharmacokinetics in normal elderly subjects. Clin Pharmacol Ther. 1988 Nov;44(5):522–530. doi: 10.1038/clpt.1988.189. [DOI] [PubMed] [Google Scholar]
  28. Slotfeldt M. L., Johnson C. E., Grambau G., Weg J. G. Reliability of theophylline clearance in determining chronic oral dosage regimens. Am J Hosp Pharm. 1979 Jan;36(1):66–68. [PubMed] [Google Scholar]
  29. Staib A. H., Harder S., Fuhr U., Wack C. Interaction of quinolones with the theophylline metabolism in man: investigations with lomefloxacin and pipemidic acid. Int J Clin Pharmacol Ther Toxicol. 1989 Jun;27(6):289–283. [PubMed] [Google Scholar]
  30. Takagi K., Hasegawa T., Yamaki K., Suzuki R., Watanabe T., Satake T. Interaction between theophylline and enoxacin. Int J Clin Pharmacol Ther Toxicol. 1988 Jun;26(6):288–292. [PubMed] [Google Scholar]
  31. Wijnands W. J., Vree T. B., Van Herwaarden C. L. Enoxacin decreases the clearance of theophylline in man. Br J Clin Pharmacol. 1985 Dec;20(6):583–588. doi: 10.1111/j.1365-2125.1985.tb05115.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wijnands W. J., Vree T. B., Van Herwaarden C. L. The effect of the 4-quinolone enoxacin on plasma theophylline concentrations. Pharm Weekbl Sci. 1986 Feb 21;8(1):42–45. doi: 10.1007/BF01975479. [DOI] [PubMed] [Google Scholar]
  33. Wijnands W. J., Vree T. B., van Herwaarden C. L. The influence of quinolone derivatives on theophylline clearance. Br J Clin Pharmacol. 1986 Dec;22(6):677–683. doi: 10.1111/j.1365-2125.1986.tb02957.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wijnands W. J., van Herwaarden C. L., Vree T. B. Enoxacin raises plasma theophylline concentrations. Lancet. 1984 Jul 14;2(8394):108–109. doi: 10.1016/s0140-6736(84)90283-6. [DOI] [PubMed] [Google Scholar]

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