Urinary excretion and bactericidal activities of gemifloxacin and ofloxacin after a single oral dose in healthy volunteers

In a randomized crossover study, 16 volunteers (8 men, 8 women) received si ngle oral doses of 320 mg of gemifloxacin and 400 mg of ofloxacin on two se parate occasions in the fasting state to assess the urinary excretion and u rinary bactericidal titers (UBTs) at intervals for up to 144 h. Ofloxacin s howed higher concentrations in urine compared with those of gemifloxacin. T he median (range) cumulative excretion of gemifloxacin was 29.7% (8.4 to 48 .7%) of the parent drug administered, and median (range) cumulative excreti on 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 a s 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 mug/ml, respectively; Klebsiella pneumoniae, 0.03 and 0.06 mug/ml, respecti vely; Proteus mirabilis, 0.125 and 0.125 mug/ml, respectively; Escherichia coli, 0.06 and 0.5 mug/ml, respectively; Pseudomonas aeruginosa, 1 and 4 mu g/ml, respectively; Staphylococcus aureus, 0.008 and 0.25 mug/ml, respectiv ely; Enterococcus faecalis, 0.06 and 2 mug/ml, respectively; Staphylococcus aureus, 0.25 and 4 mug/ml, respectively; Enterococcus faecalis, 0.5 and 32 mug/ml, respectively; and Staphylococcus aureus, 2 and 32 mug/ml, respecti vely. Generally, the UBTs for gram-positive uropathogens were higher for ge mifloxacin than for ofloxacin and the UBTs for gram-negative uropathogens w ere higher for ofloxacin than for gemifloxacin. According to the UBTs, oflo xacin-resistant uropathogens (MICs, greater than or equal to4 mg/liter) sho uld also be considered gemifloxacin resistant. Although clinical trials hav e shown that gemifloxacin is effective for the treatment of uncomplicated u rinary tract infections, whether an oral dosage of 320 mg of gemifloxacin o nce daily is also adequate for the treatment of complicated urinary tract i nfections has yet to be confirmed.