Pharmacokinetic and pharmacodynamic integration and modelling of marbofloxacin in calves for Mannheimia haemolytica and Pasteurella multocida

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 C max /MIC ratios of 45.0 and AUC 24h /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: AUC 24h /MIC ratios for no reduction, 3 log 10 and 4 log 10 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 log 10 and 4 log 10 reductions in bacterial count was smaller for P. multocida than for M. haemolytica . In conjunction with literature data on MIC 90 values, the present results allowed prediction of dosages for efficacy for each organism for the three levels of growth inhibition.