Species-independent pharmacodynamics of gemifloxacin and ciprofloxacin with Haemophilus influenzae and Moraxella catarrhalis in an in vitro dynamic model.
To demonstrate the antimicrobial effects of the different pharmacokinetics of gemifloxacin and ciprofloxacin, the pharmacodynamics of gemifloxacin and ciprofloxacin were studied using two clinical isolates each of Haemophilus influenzae and Moraxella catarrhalis. Monoexponentially decreasing concentrations of gemifloxacin (single dose, half-life 7.4 h) and ciprofloxacin (two 12-h doses, half-life 4 h) were simulated in an in vitro dynamic model over 8-fold ranges of the area under the curve (AUC)-to-MIC ratio: from 56 to 466 and 112-932 h, respectively. With each quinolone, log-linear relationships were established between the intensity of the antimicrobial effect (I(E)) and AUC/MIC. The I(E)-log AUC/MIC plots were bacterial strain- and species-independent and the gemifloxacin and ciprofloxacin plots were not superimposable. To generalize the findings obtained with the studied organisms, the effects of gemifloxacin and ciprofloxacin on hypothetical strains of H. influenzae and M. catarrhalis with MICs equal to the respective MIC(90)s were predicted. Based on these predictions, the AUC/MIC(90)s of 320 mg gemifloxacin (800 h with H. influenzae and 400 h with M. catarrhalis) may be 31-34% more efficient than those of 2 x 500 mg ciprofloxacin (730 and 365 h, respectively). These data suggest greater efficacy of gemifloxacin against H. influenzae and M. catarrhalis relative to ciprofloxacin at clinically achievable AUC/MIC ratios.
Portnoy
Yury A
YA
Department of Pharmacokinetics and Pharmacodynamics, Gause Institute of New Antibiotics, Russian Academy of Medical Sciences, 11 Bolshaya Pirogovskaya Street, Moscow 119992, Russia.
Vostrov
Sergey N
SN
Lubenko
Irene Yu
IY
Zinner
Stephen H
SH
Firsov
Alexander A
AA
D000890:Anti-Infective Agents / Q000378:metabolism* / Q000494:pharmacology*; D019540:Area Under Curve; D002939:Ciprofloxacin / Q000378:metabolism* / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones; D000077735:Gemifloxacin; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects* / Q000378:metabolism*; D009287:Naphthyridines / Q000378:metabolism* / Q000494:pharmacology*; D013045:Species Specificity
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D002939:Ciprofloxacin; D000077735:Gemifloxacin