title: Pharmacokinetic/pharmacodynamic integration and modelling of oxytetracycline for the porcine pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida.
abstract: Pharmacokinetic-pharmacodynamic (PK/PD) integration and modelling were used to predict dosage schedules of oxytetracycline for two pig pneumonia pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida. Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined in broth and porcine serum. PK/PD integration established ratios of average concentration over 48 h (Cav0-48 h)/MIC of 5.87 and 0.27 μg/mL (P. multocida) and 0.70 and 0.85 μg/mL (A. pleuropneumoniae) for broth and serum MICs, respectively. PK/PD modelling of in vitro time-kill curves established broth and serum breakpoint values for area under curve (AUC0-24 h)/MIC for three levels of inhibition of growth, bacteriostasis and 3 and 4 log10reductions in bacterial count. Doses were then predicted for each pathogen, based on Monte Carlo simulations, for: (i) bacteriostatic and bactericidal levels of kill; (ii) 50% and 90% target attainment rates (TAR); and (iii) single dosing and daily dosing at steady-state. For 90% TAR, predicted daily doses at steady-state for bactericidal actions were 1123 mg/kg (P. multocida) and 43 mg/kg (A. pleuropneumoniae) based on serum MICs. Lower TARs were predicted from broth MIC data; corresponding dose estimates were 95 mg/kg (P. multocida) and 34 mg/kg (A. pleuropneumoniae).
authors.affiliation: Department of Comparative Biological Sciences, The Royal Veterinary College, Hatfield, UK.
authors.forename: L
authors.initials: L
authors.lastname: Dorey
authors.affiliation: Department of Comparative Biological Sciences, The Royal Veterinary College, Hatfield, UK.
authors.forename: L
authors.initials: L
authors.lastname: Pelligand
authors.affiliation: Department of Comparative Biological Sciences, The Royal Veterinary College, Hatfield, UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Comparative Biological Sciences, The Royal Veterinary College, Hatfield, UK.
authors.forename: P
authors.initials: P
authors.lastname: Lees
mesh_terms: D016977:Actinobacillus pleuropneumoniae / Q000187:drug effects* / Q000254:growth & development; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D010118:Oxytetracycline / Q000493:pharmacokinetics* / Q000494:pharmacology; D016979:Pasteurella multocida / Q000187:drug effects* / Q000254:growth & development; D011014:Pneumonia / Q000188:drug therapy / Q000662:veterinary*; D013552:Swine
chemical_list: D000900:Anti-Bacterial Agents; D010118:Oxytetracycline