Urinary Excretion and Bactericidal Activities of a Single Oral Dose of 400 Milligrams of Fleroxacin versus a Single Oral Dose of 800 Milligrams of Pefloxacin in Healthy Volunteers

Abstract

Twelve healthy volunteers participated in this randomized crossover study to compare the concentrations and recovery levels of fleroxacin and pefloxacin in urine and to assess their bactericidal activities against 12 strains of urinary pathogens with different susceptibilities over a wide range of MICs. The volunteers received a single oral dose of 400 mg of fleroxacin or 800 mg of pefloxacin. The mean cumulative renal excretion of unchanged fleroxacin,N-demethyl-fleroxacin, and N-oxide-fleroxacin accounted for 67, 7, and 6% of the total dose, respectively. The total urinary recovery of pefloxacin and the active metabolite norfloxacin was 34%. In the time-kill and the urinary bactericidal titer (UBT) studies, only the subjects’ urine not supplemented with broth was used. With most tested organisms and both quinolones it took more than 8 h to achieve a reduction in CFU of 99.9% (3 log units). Overall, there was a good correlation between UBTs and MICs for the strains. Against Escherichia coli ATCC 25922 the median UBTs were similar for both antibiotics and at least 1:8 for 96 h; against the E. coli strain for which the MIC was 0.5 μg/ml the UBT was at least 1:4 for 48 h. The UBTs of both drugs against Klebsiella pneumoniae were at least 1:16 for 72 h. The UBTs for Staphylococcus aureus (the MIC for which was 16 μg/ml) of both antibiotics were low, and in some of the samples, no bactericidal titers were observed. UBTs for Proteus mirabilis of pefloxacin are significantly higher than those of fleroxacin. For Pseudomonas aeruginosa the median UBTs were present for the 24-to-48-h interval. The same is true forEnterococcus faecalis. Against Staphylococcus saprophyticus, UBTs were present for at least 48 h with both quinolones. Overall, a single oral dose of 400 mg of fleroxacin exhibits UBTs comparable to those of 800 mg of pefloxacin. Therefore, it may be expected that half of the dose of fleroxacin gives comparable results in the treatment of urinary tract infections; this should be substantiated in comparative clinical trials.

Concentrations in plasma, urinary excretion and bactericidal activity of levofloxacin (500mg) versus ciprofloxacin (500mg) in healthy volunteers receiving a single oral dose

“…Laboratory, pharmacokinetic, UBT and AUBT data for the two drugs were compared for each individual by the paired t-test. Application of the paired t-test appears to be adequate according to our previous analysis of the respective residuals [6]. An α value equal to 0.05 was chosen to determine statistical significance.…”

“…A logarithmic serial dilution (dilution range 1:2 to 1:1024) was prepared by combining a 1:1 mixture of the urine sample and the individual's antimicrobial agent-free urine collected prior to drug administration [5,6,12]. UBTs were then determined by microdilution, with each well of the microplates containing 100 L of the prepared dilution.…”

“…For empirical antimicrobial therapy, an antibiotic agent should be chosen that includes most of the uropathogens in its antibacterial spectrum. In this regard, the fluoroquinolones in urine and the urinary bactericidal titres (UBTs) for common uropathogens were determined to approximate more closely their antibacterial activities at the site of infection [5][6][7][8]. According to animal and human studies [9,10], the efficacy of fluoroquinolones can be considered comparable if peak concentration/minimal inhibitory concentration (MIC) and area under the concentration-time curve (AUC)/MIC or minimal bactericidal concentration (MBC) ratios are in the same range.…”

Urinary concentrations and bactericidal activities of newer fluoroquinolones in healthy volunteers

“…This study was conducted to ascertain whether these antimicrobials provide similar bacterial killing over time and would thus be interchangeable for the treatment of UTIs [4,5].…”

Fluorchinolone: Einsatz bei Infektionen der Nieren und des Urogenitaltrakts

“…Nach oraler Gabe von Levofloxacin [9], Ofloxacin [40], Fleroxacin [49], Ciprofloxacin [8,48] und Gatifloxacin [65] werden hohe antibakterielle Konzentrationen im Urin und in den ableitenden Harnwegen erreicht.…”