Pharmacokinetics and pharmacodynamics of fluoroquinolones

The fluoroquinolones have moderate to excellent bioavailability, moderate to long elimination half-lives (50 to 98%) and volumes of distribution >1.5 L/kg. There is considerable variation in elimination pattern between fluoroquinolone agents, ranging from predominant renal excretion to extensive hepatic metabolism. Protein binding also varies between agents. Tissue concentrations often exceed plasma concentrations, while concentrations in CSF are modest in the presence of inflammation. Fluoroquinolones show concentration-dependent killing in vitro, and animal models have demonstrated the 24-hour AUC/MIC (area under the concentration-time curve/minimum inhibitory concentration) ratio to be the best predictor of bacterial killing in vivo, with the peak plasma concentration (Cmax)/MIC ratio being important for some bacteria, to prevent the emergence of resistance during treatment. Animal models and human studies with ciprofloxacin, grepafloxacin and levofloxacin show that a 24-hour AUC/MIC ratio of about 100, or a Cmax/MIC ratio of about 10 gives maximum clinical and bacteriological efficacy. These values can be used to predict the efficacy of different agents against different pathogens, and to define pharmacodynamic 'breakpoints'.