title: 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 5.6-16.0mg/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 mgh/L (range 66.2-96.8 mgh/L) (fAUC 59.8+/-9.9) and serum half-life (t(1/2)) 6.7+/-0.5h. Mean urine concentrations were 88.0+/-100mg/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, 12100+/-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.
authors.affiliation: Department of Internal Medicine, University of Manitoba, Winnipeg, Canada. Inicolle@hsc.mb.ca
authors.forename: Lindsay
authors.initials: L
authors.lastname: Nicolle
authors.forename: Heather
authors.initials: H
authors.lastname: Duckworth
authors.forename: Dan
authors.initials: D
authors.lastname: Sitar
authors.forename: Lisa
authors.initials: L
authors.lastname: Bryski
authors.forename: Godfrey
authors.initials: G
authors.lastname: Harding
authors.forename: George
authors.initials: G
authors.lastname: Zhanel
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D004927:Escherichia coli Infections / Q000188:drug therapy*; D005260:Female; D006801:Humans; D064704:Levofloxacin; D015242:Ofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011704:Pyelonephritis / Q000188:drug therapy*; D044967:Serum / Q000737:chemistry; D013997:Time Factors; D014556:Urine / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin