Pharmacokinetic and pharmacodynamic integration and modelling of marbofloxacin in calves for Mannheimia haemolytica and Pasteurella multocida |
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| Authors: | T Potter J Illambas L Pelligand A Rycroft P Lees |
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| Institution: | 1. Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA;2. Athens Veterinary Diagnostic Laboratory, College of Veterinary Medicine, University of Georgia, Athens, Georgia;3. USDA/ARS/NADC, Ames, Iowa, USA;1. Clinical Bacteriology Laboratory, Indian Veterinary Research Institute (IVRI), Mukteswar 263138, Nainital (District), Uttarakhand (UK), India;2. Division of Virology, Indian Veterinary Research Institute (IVRI), Mukteswar 263138, Nainital (District), Uttarakhand (UK), India;3. Division of Bacteriology and Mycology, Indian Veterinary Research Institute (IVRI), Izatnagar 243122, Uttar Pradesh (UP), India;1. US Department of Agriculture, National Animal Disease Center, 1920 Dayton Avenue, Ames, IA 50010, USA;2. Department of Veterinary Biosciences, University of Minnesota, St. Paul, MN 55108, USA;1. Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium;2. Department of Internal Medicine and Clinical Biology of Large Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium |
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| Abstract: | The pharmacokinetics (PK) and pharmacodynamics (PD) of marbofloxacin were established in calves for six strains of each of the pneumonia pathogens Mannheimia haemolytica and Pasteurella multocida. The distribution of marbofloxacin into inflamed (exudate) and non-inflamed (transudate) tissue cage fluids allowed comparison with the serum concentration–time profile. To establish the PD profile, minimum inhibitory concentration (MIC) was determined in Mueller–Hinton broth (MHB) and calf serum.Moderately higher MICs were obtained for serum compared to MHB. An initial integration of PK–PD data established Cmax/MIC ratios of 45.0 and AUC24h/MIC values of 174.7 h, based on serum MICs, for both bacterial species. Using bacterial time-kill curves, generated ex vivo for serum marbofloxacin concentrations, PK–PD modelling established three levels of growth inhibition: AUC24h/MIC ratios for no reduction, 3 log10 and 4 log10 reductions in bacterial count from the initial inoculum count were 41.9, 59.5 and 68.0 h for M. haemolytica and 48.6, 64.9 and 74.8 h for P. multocida, on average respectively. Inter-strain variability for 3 log10 and 4 log10 reductions in bacterial count was smaller for P. multocida than for M. haemolytica. In conjunction with literature data on MIC90 values, the present results allowed prediction of dosages for efficacy for each organism for the three levels of growth inhibition. |
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