Comparative pharmacokinetics of norfloxacin-glycine acetate after single oral administration and medication with drinking water in broilers

  • Lim, Jong-hwan (College of Veterinary Medicine, Chungnam National University) ;
  • Lim, Byoung-yong (College of Veterinary Medicine, Chungnam National University) ;
  • Park, Byung-kwon (College of Veterinary Medicine, Chungnam National University) ;
  • Kim, Myong-seok (College of Veterinary Medicine, Chungnam National University) ;
  • Jang, Beom-su (College of Veterinary Medicine, Chungnam National University) ;
  • Park, Seung-chun (College of Veterinary Medicine, Kyungpook National University) ;
  • Yun, Hyo-in (College of Veterinary Medicine, Chungnam National University)
  • Accepted : 2004.04.02
  • Published : 2004.06.30


Norfloxacin (NFX) is a fluorquinolone antibacterial agent with a high antimicrobial activity and might have great potential for treating common infections in poultry. The objective of this study was to obtain comparative pharmacokinetic data after a single oral administration and medication with drinking water of norfloxacin-glycine acetate (NFX-GA) at the dose rate of 10 mg/kg bw in broilers. Fifty minutes following oral administration of NFX-GA, serum concentrations peaked at $1.32{\mu}g/mL$ (range $1.03-1.45{\mu}g/mL$). Serum concentration of NFX declined with a half-life of $7.21{\pm}1.81$ h. On the third day after administration of medicated drinking water, steady-state was reached, with mean concentrations of NFX of $0.70{\pm}0.35{\mu}g/mL$. The concentration of NFX after medication of NFX-GA with drinking for 3 days provides sufficient levels to obtain maximum therapeutic effects and maintains the serum persistence of concentration exceeding MIC.


  1. Alkaysi, H. N., Abdel-Hay, M. H., Sheikh Salem, M., Gharaibeh, A. M. and Nawas, T. E. Chemical and microbiological investigations of metal ion nteraction with norfloxacin. Int. J. Pharm. 1992, 87, 73-77
  2. Anadón, A., Martínez-Larrañaga, M. R., Velez, C., Díaz, M. J. and Bringas, P. Pharmacokinetics of norfloxacin and its N-desethyl and oxo-metabolites in broiler chickens. Am. J. Vet. Res. 1992, 53, 2084-2089
  3. Appelbaum, P. C. and Hunter, P. A. The fluoroquinolone antibacterials: past, present and future perspectives. Int. J. Antimicrob. Agents. 2000, 16, 5-15
  4. Ballesteros, O., Toro, I., Sanz-Nebot, V., Navalon, A., Vilchez, J. L. and Barbosa, J. Determination of fluoroquinolones in human urine by liquidchromatography coupled to pneumatically assisted electrospray ionization mass spectrometry. J. Chromatogr. A. 2003, 798, 137-144
  5. Cordoba-Borrego, M., Cordoba-Diaz, M. and Cordoba-Diaz, D. Validation of a high-performance liquid chromatographic method for the determination ofnorfloxacin and its application to stability studies (photo-stability study of norfloxacin). J. Pharm. Biomed. Anal. 1999, 18, 919-926
  6. Crumplin, G. C., Kenwright, M. and Hurst, T. Investigations into the mechanism of action of the antibacterial agent norfloxacin. J. Antimicrob. Chemother. 1984, 13(Suppl. B), 9-23
  7. Dorrestein, G. M. Formulation and bioavailability problems of drug formulations in birds. J. Vet. Pharmacol. Ther. 1992, 15, 143-150
  8. Fawaz, F., Bonini, F., Guyot, M., Bildet, J., Maury, M. and Lagueny, A. M. Bioavailability of norfloxacin from PEG 6000 solid dispersion and cyclodextrininclusion complexes in rabbits. Int. J. Pharm. 1996, 132, 271-275
  9. Fierens, C., Hillaert, S. and Van den Bossche, W. The qualitative and quantitative determination of quinolones of first and second generation by capillary electrophoresis. J. Pharm. Biomed. Anal., 2000, 22, 763-772
  10. Ganiere, J. P., Hervouet, P., Delaporte, J. and Froyman, R. Serum kinetics of enrofloxacin in chickens during continuous drinking water medication. J. Vet.Pharmacol. Ther. 1997, 20(Suppl. 1), 202-203
  11. Guyot, M., Fawaz, F., Bildet, J., Bonini, F. and Lagueny, A. M. Physicochemical characterization and dissolution of norfloxacin/cylodextrin inclusion compounds and PEG solid dispersions. Int. J. Pharm. 1995, 123, 53-63
  12. Laczay, P., Semjén, G., Nagy, G. and Lehel, J. Comparative studies on the pharmacokinetics of norfloxacin in chickens, turkeys and geese after a singleoral administration. J. Vet. Pharmacol. Ther. 1998, 21, 161-164
  13. Madaras-Kelly, K. J., Ostergaard, B. E., Backer, H. L. and Rotschafer, J. C. Twenty-four-hour area under the concentration-time curve/MIC ratio as a generic predictor of fluoroquinolone antimicrobial effect using three strains of Pseudomonas aeruginosa and in vitro pharmacodynamic model. Antimicrob. Agents. Chemother. 1996, 40, 627-632
  14. Mascher, H. J. and Kikuta, C. Determination of norfloxacin in human plasma and urine by highperformance liquid chromatography and fluorescence detection. J. Chromatogr. A. 1998, 812, 381-385
  15. Meinen, J. B., McClure, J. T. and Rosin, E. Pharmacokinetics of enrofloxacin in clinically normal dogs and mice and drug pharmacodynamics in neutropenic mice with Escherichia coli and staphylococcal infections. Am. J. Vet. Res. 1995, 56, 1219-1224
  16. Neu, H. C. and Labthavikul, P. In vitro activity of norfloxacin, a quino-linecarboxilic acid, compared with that of b-lactams, aminoglycosides, and trimethoprim. Antimicrob. Agents. Chemother. 1982, 22, 23-27
  17. Norrby, S. R. and Jonsson, M. Antibacterial activity of norfloxacin. Antimicrob. Agents. Chemother. 1983, 23, 15-18
  18. Park, S. C. and Yun. H. I. Clinical pharmacokinetics of norfloxacin-glycine acetate after intravenous and intramuscular administration to horses. Res. Vet. Sci. 2003, 74, 79-83
  19. Raemdonck, D. L., Tanner, A. C., Tolling, S. T. and Michener, S. L. In vitro susceptibility of avian Escherichia coli and Pasteurella multocida to danofloxacin and five other antimicrobials. Avian Dis. 1992, 36, 964-967
  20. Santos, M. D. F., Vermeersch, H., Remon, J. P., Schelkens, M., De Backer, P., Ducatelle, R. and Haesebrouck, F. Administration of doxycycline hydrochloride via drinking water to turkeys under laboratory and field conditions. Poult. Sci. 76, 1342-1348
  21. Scheer, M, de Jong, A, Froyman, R. and Heinen, E. Antimicrobial activity in the digestive tract of broiler chickens treated orally with enrofloxacin. J. Vet. Pharmacol. Ther. 1997, 20(Suppl.1), 201-202
  22. Schneider, M. J. and Donoghue, D. J. Multiresidue analysis of fluoroquinolone antibiotics in chicken tissue using liquid chromatography-fluorescence-multiple mass spectrometry. J. Chromatogr. B. 2002, 780, 83-92
  23. Vermeulen, B., De Backer, P. and Remon, J. P. Drug administration to poultry. Adv. Drug Deliv. Rev. 2002, 54, 795-803
  24. Wallis, S. C., Charles, B. G., Gahan, L. R., Filippich, L. J., Bredhauer, M. G. and Duckworth, P. A. Interaction of norfloxacin with divalent and trivalentpharmaceutical cations. In vitro complexation and in vivo pharmacokinetic studies in the dog. J. Pharm. Sci. 1996, 85, 803-809