A tissue cage model in calves for studies on pharmacokinetic/pharmacodynamic interactions of antimicrobials.

An in vivo model for studies of pharmacokinetic/pharmacodynamic (PK/PD) interactions of antimicrobials was developed. Tissue cages with a constant surface area but with different volumes were implanted in calves and infected with Mannheimia haemolytica. Penicillin was injected directly into the cages. With this procedure, different concentration-time profiles could be simulated so that the effect of a range of PK/PD indices on the infection could be monitored. The area under the curve to minimum inhibitory concentration (MIC) and time above MIC were equally predictive for effect, but Cmax to MIC was not. If drug dosages in relation to the MIC of strains used for infection are optimised, the model offers an interesting alternative to explore relevant factors for drug dosage optimisation.