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Antimicrobial Agents and Chemotherapy, February 2003, p. 626-635, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.626-635.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics (PK), Pharmacodynamics (PD), and PK-PD Integration of Danofloxacin in Sheep Biological Fluids

F. Shojaee Aliabadi,1 M. F. Landoni,2 and P. Lees3*

Department of Veterinary Basic Sciences, The Royal Veterinary College, Hawkshead Campus, North Mymms, Hatfield, Hertfordshire AL9 7TA, United Kingdom,3 Food Quality Control Laboratory, Khatam Co., Tehran, Iran,1 Facultade de Ciencias Veterinarias, Universidad Nacional de la Plata, CC2916, (1900) La Plata, Argentina2

Received 18 October 2001/ Returned for modification 19 August 2002/ Accepted 7 November 2002

The fluoroquinolone antimicrobial drug danofloxacin was administered to sheep intravenously (i.v.) and intramuscularly (i.m.) at a dose of 1.25 mg/kg of body weight in a two-period crossover study. The pharmacokinetic properties of danofloxacin in serum, inflamed tissue cage fluid (exudate), and noninflamed tissue cage fluid (transudate) were established by using a tissue cage model. The in vitro and ex vivo activities of danofloxacin in serum, exudate, and transudate against a pathogenic strain of Mannheimia haemolytica were established. Integration of in vivo pharmacokinetic data with the in vitro MIC provided mean values for the area under the curve (AUC)/MIC for serum, exudate, and transudate of 60.5, 85.6, and 45.7 h, respectively, after i.v. dosing and 55.9, 77.9, and 49.1 h, respectively, after i.m. dosing. After i.m. dosing, the maximum concentration/MIC ratios for serum, exudate, and transudate were 10.8, 3.0, and 1.6, respectively. The ex vivo growth inhibition data after i.m. dosing were fitted to the inhibitory sigmoid Emax equation to provide the values of AUC/MIC required to produce bacteriostasis, bactericidal activity, and elimination of bacteria. The respective values for serum were 17.8, 20.2, and 28.7 h, and slightly higher values were obtained for transudate and exudate. It is proposed that use of these data might provide a novel approach to the rational design of dosage schedules.

* Corresponding author. Mailing address: Department of Veterinary Basic Sciences, The Royal Veterinary College, Hawkshead Campus, North Mymms, Hatfield, Hertfordshire AL9 7TA, United Kingdom. Phone: 44 1707 666294. Fax: 44 1707 666371. E-mail: plees{at}rvc.ac.uk.

Antimicrobial Agents and Chemotherapy, February 2003, p. 626-635, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.626-635.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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