Pharmacokinetics and pharmacodynamics of fluoroquinolones
Abstract
The pharmacokinetic characteristics of levofloxacin, moxifloxacin, and gatifloxacin include excellent oral bioavailability (90-99%), extensive penetration into tissues and body fluids, and an elimination half-life (6-12 hrs) that allows for once-daily dosing in patients with normal renal function. Levofloxacin and gatifloxacin primarily are excreted unchanged in the urine, whereas moxifloxacin undergoes hepatic metabolism. The pharmacodynamic values that correlate with successful clinical and microbiologic outcomes, as well as prevent emergence of bacterial resistance, are ratios of maximum or peak unbound drug concentration (Cmax) to minimum inhibitory concentration (MIC), and 24-hour unbound area under the concentration curve (AUC(0-24hr)) to MIC. For gram-negative infections, a Cmax:MIC greater than or equal to 10 and AUC(0-24hr):MIC greater than or equal to 125 are associated with increased probability of a successful outcome. For infections caused by Streptococcus pneumoniae, an AUC(0-24hr):MIC of 30 or more is suggested for favorable clinical outcomes. Pharmacokinetic and pharmacodynamic values influence rational therapeutic decisions in the selection and dosages of these drugs.
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