Development and validation of an in vivo model for pharmacokinetic/pharmacodynamic studies of antimicrobials in domestic animals

Abstract

The increase in bacterial resistance to antimicrobials has motivated researchers to develop experimental animal models to integrate pharmacokinetic/pharmacodynamic (PK/ PD) profiles to predict the effectiveness of antimicrobials treatments. The models used to date have a weakness based on the use of the minimum inhibitory concentration (MIC), whose value is obtained only in vitro , determined under constant conditions with an exponential error, regarding to the double dilution used. The aim of this study was to develop and validate a device for subcutaneous implantation, which can be applied in any animal species, allowing simultaneous description of in vivo bacterial killing curve and pharmacokinetic profile of the drug under study. Based on the obtained results, it can be concluded that the use of this model will allow researchers to apply PK/ PD decreasing the error originated in the use of MIC as a measure of antimicrobial pharmacodynamics.