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Pharmacokinetic and pharmacodynamic profiles of danofloxacin administered by two dosing regimens in calves infected with Mannheimia (Pasteurella) haemolytica.

Abstract
The pharmacokinetics and pharmacodynamics of danofloxacin in calves with induced Mannheimia (Pasteurella) haemolytica pneumonia were evaluated. Calves received either saline as an intravenous (IV) bolus or danofloxacin (0.738 mg/kg of body weight) administered as either a single IV bolus or a 36-h continuous IV infusion. Blood samples and bronchial secretions were collected before and at predetermined times over 48 h following the start of treatment. Calves were assessed clinically throughout, and lung consolidation was assessed at necropsy. Bronchial secretions and lung tissue were cultured for M. haemolytica. Bolus administration of danofloxacin produced a high maximum drug concentration-to-MIC ratio (C(max):MIC) of 14.5 and a time period of 9.1 h when plasma danofloxacin concentrations exceeded the MIC (T>MIC). Following danofloxacin infusion, the C(max):MIC was low (2.3), with a long T>MIC (33.3 h). The area under the curve-to-MIC ratios were 43.3 and 49.1 for the bolus and infusion administrations, respectively. The single bolus of danofloxacin was more effective than the same dose administered by continuous infusion, as indicated by a significantly lower (P < 0.05) number of animals with M. haemolytica in bronchial secretions after treatment and lower rectal temperatures in the 24 h after the start of treatment. Thus, danofloxacin exhibited concentration-dependent antimicrobial activity in cattle with respiratory disease caused by M. haemolytica.
AuthorsPatxi Sarasola, Peter Lees, Fariborz Shojaee AliAbadi, Quintin A McKellar, William Donachie, Kate A Marr, Simon J Sunderland, Tim G Rowan
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 46 Issue 9 Pg. 3013-9 (Sep 2002) ISSN: 0066-4804 [Print] United States
PMID12183261 (Publication Type: Journal Article)
Chemical References
  • Anti-Infective Agents
  • Fluoroquinolones
  • danofloxacin
Topics
  • Animals
  • Anti-Infective Agents (administration & dosage, pharmacokinetics, therapeutic use)
  • Area Under Curve
  • Dogs
  • Fluoroquinolones
  • Infusions, Intravenous
  • Injections, Intravenous
  • Lung (microbiology)
  • Male
  • Mannheimia haemolytica (drug effects)
  • Pasteurella Infections (drug therapy, microbiology, physiopathology)
  • Pneumonia, Bacterial (drug therapy, microbiology, physiopathology)
  • Respiratory Mechanics (drug effects)

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