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Pharmacokinetic/pharmacodynamic integration and modelling of oxytetracycline for the porcine pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida
Author(s) -
Dorey L.,
Pelligand L.,
Cheng Z.,
Lees P.
Publication year - 2017
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12385
Subject(s) - pasteurella multocida , actinobacillus pleuropneumoniae , microbiology and biotechnology , oxytetracycline , pharmacokinetics , pharmacodynamics , minimum inhibitory concentration , tar (computing) , chemistry , antibiotics , biology , bacteria , pharmacology , serotype , computer science , programming language , genetics
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 ( C av0–48 h )/ MIC of 5.87 and 0.27 μ g/mL ( P. multocida ) and 0.70 and 0.85 μ g/mL ( A. pleuropneumoniae ) for broth and serum MIC s, respectively. PK / PD modelling of in vitro time–kill curves established broth and serum breakpoint values for area under curve ( AUC 0–24 h )/ MIC for three levels of inhibition of growth, bacteriostasis and 3 and 4 log 10 reductions 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 MIC s. Lower TAR s were predicted from broth MIC data; corresponding dose estimates were 95 mg/kg ( P. multocida ) and 34 mg/kg ( A. pleuropneumoniae ).