Correlation between pharmacokinetics, pharmacodynamics and efficacy of antibacterial agents in animal models.
On the basis of a review of published literature it is demonstrated that pharmacokinetic parameters of antibacterial agents correlate well with therapeutic efficacy in animal models, provided pharmacodynamic parameters are taken into account. The time that serum levels exceed the MIC is the most significant parameter determining efficacy of beta-lactams, whereas the efficacy of aminoglycosides is dependent on serum concentrations and the area under the curve. The efficacy of quinolones tends to be correlated to the doses administered or drug levels achieved. However, specific pharmacodynamic properties contribute significantly to the therapeutic efficacy of a few quinolones only whereas other quinolones lack these specific pharmacodynamic attributes. Thus, the correlation of pharmacokinetic parameters with therapeutic efficacy provides important basic concepts for the design of preclinical and clinical studies in the course of which additional pharmacodynamic properties will become apparent.
Dalhoff
A
A
Abteilung für Medizinische Mikrobiologie, Klinikum der Christian-Albrechts-Universität, Kiel, FRG.
Ullmann
U
U
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001424:Bacterial Infections / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D008826:Microbial Sensitivity Tests
D000900:Anti-Bacterial Agents