In a randomized crossover study, 16 volunteers (8 men, 8 women) received single oral doses of 320 mg of
gemifloxacin and 400 mg of
ofloxacin on two separate occasions in the fasting state to assess the urinary excretion and urinary bactericidal titers (UBTs) at intervals for up to 144 h.
Ofloxacin showed higher concentrations in urine compared with those of
gemifloxacin. The median (range) cumulative excretion of
gemifloxacin was 29.7% (8.4 to 48.7%) of the parent
drug administered, and median (range) cumulative excretion of
ofloxacin was 84.3% (46.5 to 95.2%) of the parent
drug administered. The UBTs, i.e., the highest twofold dilutions (with
antibiotic-free urine as the diluent) of urine that were still bactericidal, were determined for a reference strain and nine uropathogens for which the MICs of
gemifloxacin and
ofloxacin were as follows: Escherichia coli ATCC 25922, 0.016 and 0.06 microg/ml, respectively; Klebsiella pneumoniae, 0.03 and 0.06 microg/ml, respectively; Proteus mirabilis, 0.125 and 0.125 microg/ml, respectively; Escherichia coli, 0.06 and 0.5 microg/ml, respectively; Pseudomonas aeruginosa, 1 and 4 microg/ml, respectively; Staphylococcus aureus, 0.008 and 0.25 microg/ml, respectively; Enterococcus faecalis, 0.06 and 2 microg/ml, respectively; Staphylococcus aureus, 0.25 and 4 microg/ml, respectively; Enterococcus faecalis, 0.5 and 32 microg/ml, respectively; and Staphylococcus aureus, 2 and 32 microg/ml, respectively. Generally, the UBTs for gram-positive uropathogens were higher for
gemifloxacin than for
ofloxacin and the UBTs for gram-negative uropathogens were higher for
ofloxacin than for
gemifloxacin. According to the UBTs,
ofloxacin-resistant uropathogens (MICs, >or=4 mg/liter) should also be considered
gemifloxacin resistant. Although clinical trials have shown that
gemifloxacin is effective for the treatment of uncomplicated
urinary tract infections, whether an oral dosage of 320 mg of
gemifloxacin once daily is also adequate for the treatment of complicated
urinary tract infections has yet to be confirmed.