Urinary Excretion and Bactericidal Activities of Gemifloxacin and Ofloxacin after a Single Oral Dose in Healthy Volunteers

Abstract

ABSTRACT 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 μg/ml, respectively; Klebsiella pneumoniae , 0.03 and 0.06 μg/ml, respectively; Proteus mirabilis , 0.125 and 0.125 μg/ml, respectively; Escherichia coli , 0.06 and 0.5 μg/ml, respectively; Pseudomonas aeruginosa , 1 and 4 μg/ml, respectively; Staphylococcus aureus , 0.008 and 0.25 μg/ml, respectively; Enterococcus faecalis , 0.06 and 2 μg/ml, respectively; Staphylococcus aureus , 0.25 and 4 μg/ml, respectively; Enterococcus faecalis , 0.5 and 32 μg/ml, respectively; and Staphylococcus aureus , 2 and 32 μg/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, ≥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.