title: Pharmacokinetics (PK), pharmacodynamics (PD), and PK-PD integration of danofloxacin in sheep biological fluids.
abstract: 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 E(max) 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.
authors.affiliation: Department of Veterinary Basic Sciences, The Royal Veterinary College, Hawkshead Campus, North Mymms, Hatfield, Hertfordshire AL9 7TA, United Kingdom.
authors.forename: F Shojaee
authors.initials: FS
authors.lastname: Aliabadi
authors.forename: M F
authors.initials: MF
authors.lastname: Landoni
authors.forename: P
authors.initials: P
authors.lastname: Lees
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D018592:Cross-Over Studies; D024841:Fluoroquinolones; D006207:Half-Life; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D016978:Mannheimia haemolytica / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D012756:Sheep; D014018:Tissue Distribution
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; C068581:danofloxacin