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Pharmacodynamics of oxytetracycline administered alone and in combination with carprofen in calves
  1. C. Brentnall1,
  2. Z. Cheng1,
  3. Q. A. McKellar1 and
  4. P. Lees1
  1. 1Department of Veterinary Basic Sciences, The Royal Veterinary College, Hawskhead Campus, Hatfield, Hertfordshire AL9 7TA, UK
  2. 2Q. A. McKellar is also at University of Hertfordshire, Hatfield, Hertfordshire AL10 9AB, UK
  1. E-mail for correspondence:zcheng{at}rvc.ac.uk

The pharmacodynamics (PD) of oxytetracycline was investigated against a strain of Mannheimia haemolytica. In vitro measurements, comprising minimum inhibitory concentration (MIC), minimum bactericidal concentration and time-kill curves, were conducted in five matrices; Mueller Hinton Broth (MHB), cation-adjusted MHB (CAMHB) and calf serum, exudate and transudate. MICs were much higher in the biological fluids than in MHB and CAMHB. Ratios of MIC were, serum: CAMHB 19 : 1; exudate:CAMHB 16.1; transudate:CAMHB 14 : 1. Ex vivo data, generated in the tissue cage model of inflammation, demonstrated that oxytetracycline, administered to calves intramuscularly at a dose rate of 20 mg/kg, did not inhibit the growth of M haemolytica in serum, exudate and transudate, even at peak concentration. However, using in vitro susceptibility in CAMHB and in vivo-determined pharmacokinetic (PK) variables, average and minimum oxytetracycline concentrations relative to MIC (Cav/MIC and Cmin/MIC) predicted achievement of efficacy for approximately 48 hours after dosing. Similar Cav/MIC and Cmin/MIC data were obtained when oxytetracycline was administered in the presence of carprofen. PK-PD integration of data for oxytetracycline, based on MICs determined in the three biological fluids, suggests that it possesses, at most, limited direct killing activity against M haemolytica. These data raise questions concerning the mechanism(s) of action of oxytetracycline, when administered at clinically recommended dose rates.

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  • Provenance not commissioned; externally peer reviewed

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