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. 1990 Sep;34(9):1739–1743. doi: 10.1128/aac.34.9.1739

Effects of enoxacin on renal and metabolic clearance of theophylline in rats.

M Nadai 1, T Hasegawa 1, T Kuzuya 1, I Muraoka 1, K Takagi 1, H Yoshizumi 1
PMCID: PMC171915  PMID: 2285287

Abstract

The effects of enoxacin and its metabolite 4-oxoenoxacin on the disposition of theophylline were investigated in rats. Systemic clearance of theophylline was significantly decreased by approximately 40, 46, and 50% after oral coadministration of 25, 100, and 200 mg of enoxacin per kg, respectively. No significant changes in the volume of distribution of theophylline were observed. 4-Oxoenoxacin had no direct effect on theophylline disposition. Significant changes in urinary excretion of theophylline and its metabolites were observed. (i) Urinary excretion of unchanged theophylline was significantly increased in proportion to increases in enoxacin dosage. (ii) Decreases in renal clearance of theophylline and metabolic clearance of 1-methyluric acid and 1,3-dimethyluric acid were observed. (iii) The percent decreases in the metabolic clearance of 1-methyluric acid were dependent on enoxacin dosage. It is likely that enoxacin inhibits the elimination process, which depends on cytochrome P-450-mediated isozymes for N demethylation and oxidation, and that the capacity of the inhibitory effect of enoxacin is greater in the N-demethylation pathway than it is in oxidation.

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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. Campbell M. E., Grant D. M., Inaba T., Kalow W. Biotransformation of caffeine, paraxanthine, theophylline, and theobromine by polycyclic aromatic hydrocarbon-inducible cytochrome(s) P-450 in human liver microsomes. Drug Metab Dispos. 1987 Mar-Apr;15(2):237–249. [PubMed] [Google Scholar]
  3. Drew R., Rowell J., Grygiel J. J. Cimetidine: a specific inhibitor of hepatic aryl hydrocarbon hydroxylase (AHH) in the rat. Res Commun Chem Pathol Pharmacol. 1981 Jul;33(1):81–93. [PubMed] [Google Scholar]
  4. Edwards D. J., Bowles S. K., Svensson C. K., Rybak M. J. Inhibition of drug metabolism by quinolone antibiotics. Clin Pharmacokinet. 1988 Sep;15(3):194–204. doi: 10.2165/00003088-198815030-00004. [DOI] [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. Grygiel J. J., Miners J. O., Drew R., Birkett D. J. Differential effects of cimetidine on theophylline metabolic pathways. Eur J Clin Pharmacol. 1984;26(3):335–340. doi: 10.1007/BF00548764. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Inaba T., Lucassen M., Kalow W. Antipyrine metabolism in the rat by three hepatic monooxygenases. Life Sci. 1980 Jun 9;26(23):1977–1983. doi: 10.1016/0024-3205(80)90629-3. [DOI] [PubMed] [Google Scholar]
  9. Lelo A., Kjellen G., Birkett D. J., Miners J. O. Paraxanthine metabolism in humans: determination of metabolic partial clearances and effects of allopurinol and cimetidine. J Pharmacol Exp Ther. 1989 Jan;248(1):315–319. [PubMed] [Google Scholar]
  10. Lohmann S. M., Miech R. P. Theophylline metabolism by the rat liver microsomal system. J Pharmacol Exp Ther. 1976 Jan;196(1):213–225. [PubMed] [Google Scholar]
  11. 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]
  12. Sano M., Kawakatsu K., Yamamoto I., Takeyama M., Yamashina H., Goto M. Inhibitory effect of enoxacin, ofloxacin and norfloxacin on renal excretion of theophylline in humans. Eur J Clin Pharmacol. 1989;36(3):323–324. doi: 10.1007/BF00558168. [DOI] [PubMed] [Google Scholar]
  13. Takagi K., Hasegawa T., Ogura Y., Suzuki R., Yamaki K., Watanabe T., Kitazawa S., Satake T. Comparative studies on interaction between theophylline and quinolones. J Asthma. 1988;25(2):63–71. doi: 10.3109/02770908809071356. [DOI] [PubMed] [Google Scholar]
  14. Thomson A. H., Thomson G. D., Hepburn M., Whiting B. A clinically significant interaction between ciprofloxacin and theophylline. Eur J Clin Pharmacol. 1987;33(4):435–436. doi: 10.1007/BF00637645. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. 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]
  18. Williams J. F., Lowitt S., Szentivanyi A. Effects of phenobarbital and 3-methylcholanthrene pretreatment on the plasma half-life and urinary excretion profile of theophylline and its metabolites in rats. Biochem Pharmacol. 1979 Oct 1;28(19):2935–2940. doi: 10.1016/0006-2952(79)90589-6. [DOI] [PubMed] [Google Scholar]

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