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 ciprofloxacin (CIP) on Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, 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) were 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 equivalent 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 dose of GEM (320 mg) on a hypothetical strain of S. aureus with MICs=MIC(50)s would be as high as 2 x 3200 mg.
Firsov
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Department of Pharmacokinetics, Centre for Science & Technology LekBioTech, 8 Nauchny Proezd, Moscow 117246, Russia. firsov@dol.ru
Zinner
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SH
Lubenko IYu
Vostrov
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D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000378:metabolism; D024841:Fluoroquinolones; D000077735:Gemifloxacin; D006801:Humans; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009287:Naphthyridines / Q000493:pharmacokinetics / Q000494:pharmacology*; D011237:Predictive Value of Tests; D013203:Staphylococcal Infections / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects*
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D002939:Ciprofloxacin; D000077735:Gemifloxacin