Pharmacokinetics/pharmacodynamics of levofloxacin 750 mg once daily in young women with acute uncomplicated pyelonephritis

Abstract

This pilot study was undertaken to characterise the pharmacokinetics, pharmacodynamics and potential clinical efficacy of levofloxacin 750 mg once daily for 5 days for treatment of women with acute uncomplicated pyelonephritis. Four women diagnosed with acute pyelonephritis were enrolled. Following pre-therapy specimen collection, an initial oral dose of 750 mg levofloxacin was administered. The mean pharmacokinetic parameters for the first dose were: maximum serum concentration ( C max) 12.5 ± 4.7 mg/L (range 5.6–16.0 mg/L) ( fC max 8.8 ± 3.3, where f indicates the levofloxacin free or non-protein-bound fraction), area under the serum concentration–time curve (AUC) 85.4 ± 14.1 mg h/L (range 66.2–96.8 mg h/L) ( fAUC 59.8 ± 9.9) and serum half-life ( t 1/2) 6.7 ± 0.5 h. Mean urine concentrations were 88.0 ± 100 mg/L at the 0–3 h collection, 307 ± 143 mg/L at 3–6 h, 170 ± 107 mg/L at 6–12 h and 85 ± 8 mg/L at 12–24 h. Mean levofloxacin serum pharmacodynamics for infecting Escherichia coli were: C max/minimum inhibitory concentration (MIC) 323 ± 185 ( fC max/MIC 226 ± 129); and AUC/MIC 2339 ± 830 ( fAUC/MIC 1647 ± 579). Mean urine levofloxacin concentration/MIC ratios were: 900 ± 1389 for 0–3 h, 12 100 ± 4950 for 3–6 h, 5922 ± 3912 for 6–12 h and 2233 ± 1037 for 12–24 h. Levofloxacin eradicated E. coli from the urine by 3–6 h after the first dose. Levofloxacin 750 mg once daily for 5 days has pharmacodynamics that support further evaluation of this regimen for treatment of women with acute uncomplicated pyelonephritis.