Pharmacokinetic and pharmacodynamic surrogate markers: studies with fluoroquinolones in patients

Several relevant studies of fluoroquinolones are reviewed, and the pneumonia model is used to predict clinical efficacy. In vitro pharmacokinetic and pharmacodynamic relationships help the clinician understand the pharmacologic effects of an antimicrobial agent. The clinical translation of in vitro determinants has proved challenging, however. Surrogate markers that define specific relationships between pharmacokinetic and pharmacodynamic characteristics of antimicrobials have been used to predict positive patient outcomes. Studies have shown that the ratio of the area under the serum concentration-time curve from 0 to 24 hours to the minimum inhibitory concentration, also known as the area under the inhibitory curve, is uniquely suited as a surrogate for identifying fluoroquinolone concentrations that correlate with clinical efficacy. In patients, appropriate dosage levels can be readily examined with the nosocomial pneumonia model. Modeling patient responses to infection has become a useful way of interpreting the clinical effects of fluoroquinolone therapy.