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Antimicrobial Agents and Chemotherapy, September 2002, p. 3013-3019, Vol. 46, No. 9
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.9.3013-3019.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Pharmacokinetic and Pharmacodynamic Profiles of Danofloxacin Administered by Two Dosing Regimens in Calves Infected with Mannheimia (Pasteurella) haemolytica

Patxi Sarasola,¹ Peter Lees,² Fariborz Shojaee AliAbadi,^3, Quintin A. McKellar,⁴ William Donachie,⁴ Kate A. Marr,⁵ Simon J. Sunderland,^5* and Tim G. Rowan⁵

Ondax Scientific, 20280 Hondarribia, Gipuzkoa, Spain,¹ Ministry of Jahad-e-Keshavarzi, Veterinary Organisation of I. R. Iran, Tehran, Iran,³ The Royal Veterinary College, Hawkshead Campus, North Mymms, Hatfield, Hertfordshire,² The Moredun Foundation, Pentlands Science Park, Bush Loan, Penicuik, Midlothian,⁴ Pfizer Global Research and Development, Sandwich, Kent, United Kingdom⁵

Received 20 September 2001/ Returned for modification 2 April 2002/ Accepted 8 June 2002

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.

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* Corresponding author. Mailing address: Global Research and Development, Pfizer Ltd., Sandwich, Kent, CT13 9NJ United Kingdom. Phone: 44 1304 646617. Fax: 44 1304 651251. E-mail: simon_sunderland{at}sandwich.pfizer.com.

Present address: The Royal Veterinary College, Hawkshead Campus, North Mymms, Hatfield, Hertfordshire, United Kingdom.

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Antimicrobial Agents and Chemotherapy, September 2002, p. 3013-3019, Vol. 46, No. 9
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.9.3013-3019.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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