No abstract

Gatifloxacin (GTX), a new fluoroquinolone with extended antibacterial activity, is an interesting candidate for the treatment of chronic bacterial prostatitis (CBP). Besides the antibacterial spectrum, the concentrations in the target tissues and fluids are crucial for the treatment of CBP. Thus, it was of interest to investigate its penetration into prostatic and seminal fluid. GTX concentrations in plasma, urine, ejaculate, prostatic and seminal fluid, and sperm cells were determined by a high-performance liquid chromatography method after oral intake of a single 400-mg dose in 10 male Caucasian volunteers in the fasting state. Simultaneous application of the renal contrast agent iohexol was used to estimate the maximal possible contamination of ejaculate and prostatic and seminal fluid by urine. GTX was well tolerated. The means (standard deviations) for the following parameters were as indicated: time to maximum concentration of drug in serum, 1.66 (0.91) h; maximum concentration of drug in serum, 2.90 (0.39) g/ml; area under the concentration-time curve from 0 to 24 h, 25.65 g ⅐ h/ml; and half life, 7.2 (0.90) h. Within 12 h about 50% of the drug was excreted unchanged into the urine. The mean renal clearance was 169 ml/min. The gatifloxacin concentrations in ejaculate, seminal fluid, and prostatic fluid were in the range of the corresponding plasma concentrations which were 1.92 (0.27) g/ml at approximately the same time point (4 h after drug intake). The concentrations in sperm cells (0.195, 0.076, and 0.011 g/ml) could be determined in three subjects. The good penetration into prostatic and seminal fluid, the good tolerance, and the previously reported broad antibacterial spectrum suggest that GTX may be a good alternative for the treatment of chronic bacterial prostatitis. Clinical studies should be performed to confirm this assumption.Fluoroquinolones have already been used successfully in the treatment of chronic bacterial prostatitis (CBP) and are recommended as first-line treatment for this indication (1, 6). This recommendation is based on their antibacterial activity; on their ability to penetrate into prostatic tissue, prostatic fluid, seminal fluid, and ejaculate; and on clinical studies (6). Although in about 60% of patients with symptoms of chronic prostatitis significant prostatic inflammation can be demonstrated (4), an etiologically recognized pathogen, such as Escherichia coli, Klebsiella spp., Proteus spp., Enterococcus faecalis, or Pseudomonas aeruginosa, is only isolated in up to 10% of these patients (14). In the vast majority of patients, bacterial evaluation either fails to identify a pathogen (nonbacterial prostatitis), or identifies so-called atypical bacteria, like Mycoplasma spp., Ureaplasma spp., and Chlamydia spp. These atypical pathogens are, however, not well covered by the antibacterial activity of the classical fluoroquinolones, e.g., ciprofloxacin or ofloxacin. Thus, the treatment of CBP remains a challenging issue, and new fluoroquinolones with improved antibacterial acti...

The feasibility of atmospheric pressure desorption/ionization on silicon mass spectrometry (AP-DIOS-MS) for drug analysis was investigated. It was observed that only compounds with relative high proton affinity are efficiently ionized under AP-DIOS conditions. The limits of detection (LODs) achieved in MS mode with midazolam, propranolol, and angiotensin II were 80 fmol, 20 pmol, and 1 pmol, respectively. In MS/MS mode the LODs for midazolam and propranolol were 10 fmol and 5 pmol, respectively. The good linearity (r(2) > 0.991), linear dynamic range of 3 orders of magnitude, and reasonable repeatability showed that the method is suitable for quantitative analysis.

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...