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. 1990 Nov;34(11):2148–2151. doi: 10.1128/aac.34.11.2148

Effect of ciprofloxacin on antipyrine pharmacokinetics and metabolism in rats.

A Anadón 1, M R Martinez-Larrañaga 1, M C Fernandez 1, M J Diaz 1, P Bringas 1
PMCID: PMC172015  PMID: 2073104

Abstract

The effect of ciprofloxacin pretreatment on the pharmacokinetics and metabolism of antipyrine in male rats was studied. The animals received oral antipyrine (20 mg/kg of body weight) with and without ciprofloxacin pretreatment (40 mg/kg orally once a day for 8 days). The total plasma clearance of antipyrine was decreased from 0.130 +/- 0.007 to 0.090 +/- 0.005 liter/h (mean +/- standard error of the mean) (P less than 0.01) by ciprofloxacin, while the half-life at beta (elimination) phase and the area under the concentration-time curve for antipyrine were increased from 1.90 +/- 0.22 to 2.83 +/- 0.29 h (P less than 0.05) and from 43.25 +/- 3.35 to 52.41 +/- 2.31 mg.h/liter (P less than 0.05), respectively. The urinary excretions of norantipyrine, 4-hydroxyantipyrine, and 3-hydroxymethylantipyrine decreased by 73, 43, and 54%, respectively (P less than 0.001), in the 96 h after ciprofloxacin treatment. In addition, the rate constants for formation of each of these metabolites were significantly decreased, by an average of approximately 75%. These results suggest that ciprofloxacin is capable of inhibiting oxidative metabolism. This finding could be of clinical significance for drugs that are highly dependent of metabolic pathways, such as those inhibited in this study.

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Selected References

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  1. Bax N. D., Lennard M. S., Tucker G. T. Inhibition of antipyrine metabolism by beta-adrenoceptor antagonists. Br J Clin Pharmacol. 1981 Dec;12(6):779–784. doi: 10.1111/j.1365-2125.1981.tb01306.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Campoli-Richards D. M., Monk J. P., Price A., Benfield P., Todd P. A., Ward A. Ciprofloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs. 1988 Apr;35(4):373–447. doi: 10.2165/00003495-198835040-00003. [DOI] [PubMed] [Google Scholar]
  4. Cummings A. J., Martin B. K., Park G. S. Kinetic considerations relating to the accrual and elimination of drug metabolites. Br J Pharmacol Chemother. 1967 Feb;29(2):136–149. doi: 10.1111/j.1476-5381.1967.tb01947.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Danhof M., Groot-van der Vis E., Breiner D. D. Assay of antipyrine and its primary metabolites in plasma, saliva and urine by high-performance liquid chromatography and some preliminary results in man. Pharmacology. 1979;18(4):210–223. doi: 10.1159/000137254. [DOI] [PubMed] [Google Scholar]
  6. Danhof M., van Zuilen A., Boeijinga J. K., Breimer D. D. Studies of the different metabolic pathways of antipyrine in man. Oral versus i.v. administration and the influence of urinary collection time. Eur J Clin Pharmacol. 1982;21(5):433–441. doi: 10.1007/BF00542332. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. 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]
  10. Ludwig E., Székely E., Csiba A., Graber H. The effect of ciprofloxacin on antipyrine metabolism. J Antimicrob Chemother. 1988 Jul;22(1):61–67. doi: 10.1093/jac/22.1.61. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. 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]
  14. Robson R. A., Begg E. J., Atkinson H. C., Saunders D. A., Frampton C. M. Comparative effects of ciprofloxacin and lomefloxacin on the oxidative metabolism of theophylline. Br J Clin Pharmacol. 1990 Apr;29(4):491–493. doi: 10.1111/j.1365-2125.1990.tb03669.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sano M., Yamamoto I., Ueda J., Yoshikawa E., Yamashina H., Goto M. Comparative pharmacokinetics of theophylline following two fluoroquinolones co-administration. Eur J Clin Pharmacol. 1987;32(4):431–432. doi: 10.1007/BF00543982. [DOI] [PubMed] [Google Scholar]
  16. Sarkar M., Polk R. E., Guzelian P. S., Hunt C., Karnes H. T. In vitro effect of fluoroquinolones on theophylline metabolism in human liver microsomes. Antimicrob Agents Chemother. 1990 Apr;34(4):594–599. doi: 10.1128/aac.34.4.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Slusher L. B., Vesell E. S. Cimetidine-induced reduction in gastrointestinal absorption of antipyrine and rate constants for formation of its metabolites. Clin Pharmacol Ther. 1984 May;35(5):568–575. doi: 10.1038/clpt.1984.79. [DOI] [PubMed] [Google Scholar]
  18. Staib A. H., Stille W., Dietlein G., Shah P. M., Harder S., Mieke S., Beer C. Interaction between quinolones and caffeine. Drugs. 1987;34 (Suppl 1):170–174. doi: 10.2165/00003495-198700341-00035. [DOI] [PubMed] [Google Scholar]
  19. Wijnands W. J., Vree T. B. Interaction between the fluoroquinolones and the bronchodilator theophylline. J Antimicrob Chemother. 1988 Sep;22 (Suppl 100):109–114. doi: 10.1093/jac/22.supplement_c.109. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. 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]
  23. Yamaoka K., Nakagawa T., Uno T. Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm. 1978 Apr;6(2):165–175. doi: 10.1007/BF01117450. [DOI] [PubMed] [Google Scholar]

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