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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 g/ml, respectively; Klebsiella pneumoniae, 0.03 and 0.06 g/ml, respectively; Proteus mirabilis, 0.125 and 0.125 g/ml, respectively; Escherichia coli, 0.06 and 0.5 g/ml, respectively; Pseudomonas aeruginosa, 1 and 4 g/ml, respectively; Staphylococcus aureus, 0.008 and 0.25 g/ml, respectively; Enterococcus faecalis, 0.06 and 2 g/ml, respectively; Staphylococcus aureus, 0.25 and 4 g/ml, respectively; Enterococcus faecalis, 0.5 and 32 g/ml, respectively; and Staphylococcus aureus, 2 and 32 g/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.The rationale for the use of an antimicrobial agent in the management of infectious diseases is its antibacterial activity at the site of the inflammatory process. In the case of urinary tract infection (UTI), the antibacterial spectrum of the antimicrobial agent should include not only Escherichia coli and other species of the family Enterobacteriaceae but also enterococci, staphylococci, and nonfermenting bacteria such as Pseudomonas and Acinetobacter spp. The fluoroquinolones, such as ciprofloxacin and ofloxacin or levofloxacin, which have broadspectrum antibacterial activities against most gram-negative uropathogens, and the more recent members of this class, which are active against gram-positive uropathogens, are recommended as first-line agents for the treatment of complicated and nosocomial UTIs.Gemifloxacin, a new fluoroquinolone, has a broad spectrum of activity in vitro against gram-negative bacteria such as E. coli, Proteus mirabilis, some strains of Pseudomonas aeruginosa, and Klebsiella pneumoniae, and against gram-positi...

Gemifloxacin mesylate (SB-265805-S, LB-20304a) is a potent, novel fluoroquinolone agent with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in two parallel group studies in healthy male volunteers after doses of 160, 320, 480, and 640 mg once daily for 7 days. Multiple serum or plasma and urine samples were collected on days 1 and 7 and were analyzed for gemifloxacin by high-performance liquid chromatography (HPLC)-fluorescence (study 1) or HPLC-mass spectrometry (study 2). Safety assessments included vital signs, 12-lead electrocardiogram (ECG) readings, hematology, clinical chemistry, urinalysis, and adverse experience monitoring. Gemifloxacin was rapidly absorbed, with a time to maximum concentration of approximately 1 h after dosing followed by a biexponential decline in concentration. Generally, maximum concentration and area under the concentration-time curve (AUC) increased linearly with dose after either single or repeat doses. Mean ؎ standard deviation values of AUC 0-on day 7 were 4.92 ؎ 1.08, 9.06 ؎ 2.20, 12.2 ؎ 3.69, and 20.1 ؎ 3.67 g⅐h/ml following 160-, 320-, 480-, and 640-mg doses, respectively. The terminal-phase half-life was approximately 7 to 8 h, independent of dose, and was similar following single and repeated administrations. There was minimal accumulation of gemifloxacin after multiple dosing. Approximately 20 to 30% of the administered dose was excreted unchanged in the urine. The renal clearance was 160 ml/min on average after single and multiple doses, which was slightly greater than the accepted glomerular filtration rate (approximately 120 ml/min). These data show that the pharmacokinetics of gemifloxacin are linear and independent of dose. Gemifloxacin was generally well tolerated, although one subject was withdrawn from the study after 6 days at 640 mg for mild, transient elevations of alanine aminotransferase and aspartate aminotransferase not associated with any clinical signs or symptoms. There were no other significant changes in clinical chemistry, hematology or urinalysis parameters, vital signs, or ECG readings. In conclusion, the results of these studies, combined with the antibacterial spectrum and potency, support the further investigation of once-daily administration of gemifloxacin for indications such as respiratory tract and urinary tract infections.

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