Identification of the in vivo pharmacokinetics and pharmacodynamic driver of iclaprim

Abstract

The neutropenic murine thigh infection model was used to define the pharmacokinetic/pharmacodynamic index linked to efficacy of iclaprim against Staphylococcus aureus ATCC 29213 and Staphylococcus pneumoniae ATCC 10813. The 24-h area under the curve (AUC)/MIC index was most closely linked to efficacy for S. aureus (R 2 , 0.65), while both the 24-h AUC/MIC and the percentage of time that drug concentrations remain above the MIC (%T>MIC) were strongly associated with effect (R 2 , 0.86 for both parameters) for S. pneumoniae.