Gemifloxacin and ciprofloxacin pharmacodynamics in an in-vitro dynamic model: prediction of the equivalent AUC/MIC breakpoints and doses

To compare the antimicrobial effects (AMEs) of gemifloxacin (GEM) and cipro floxacin (CIP) on Staphylococcus aureus, Escherichia coli and Pseudomonas a eruginosa, a series of pharmacokinetic profiles of GEM (a single dose with the half-life (T-1/2) of 7.4 h and CIP (two 12 h doses with T-1/2 Of 4 h) w ere simulated in vitro over eight-fold ranges of the AUC/MIC ratio. Species -and strain-independent linear relationships observed between the intensity of AME (I-E) and log AUC/MIC were not superimposed for GEM and CIP (r(2) = 0.99 and 0.98, respectively). The predicted ratio for GEM that might be eq uivalent to a clinically established breakpoint value of AUC/MIC = 125 (mg h/l)/(mg/l) for CIP was estimated at 110 (mg h/l)/(mg/l). It was calculated , that a daily dose of CIP that might provide the same AME as a clinical do se of CEM (320 mg) on a hypothetical strain of S. aureus with MICs = MIC(50 )s would be as high as 2 x 3200 mg. (C) 2000 Elsevier Science B.V. and Inte rnational Society of Chemotherapy. All rights reserved.