Concentrations of Gatifloxacin in Plasma and Urine and Penetration into Prostatic and Seminal Fluid, Ejaculate, and Sperm Cells after Single Oral Administrations of 400 Milligrams to Volunteers

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...

Pharmacokinetics and Pharmacodynamics of Gatifloxacin against Streptococcus pneumoniae and Staphylococcus aureus in a Granulocyte-Rich Exudate

“…Our pharmacokinetic results were in good agreement with those of previous studies (10,11,15,20). The MICs at which 90% of the isolates tested are inhibited (MIC 90 s) of gatifloxacin for S. pneumoniae (0.5 g/ml) (6) and methicillin-susceptible S. aureus (0.1 to 0.5 g/ml) (1) are in the range of those for our test strains.…”

The Commonest Uropathogens Causing Urinary Tract Infection Among Patients Attending a Tertiary Care Hospital in Eastern Bihar, and Their Antibiogram

“…Resistance to ciprofloxacin has emerged in a variety of genera belonging to the family Enterobacteriaceae. Our findings concur with such findings reported earlier [32,33] . Apart from the notable resistance of E. coli to ciprofloxacin, other organisms were also found to be resistant to ciprofloxacin especially K. pneumoniae, Pseudomonas spp., Proteus spp., Enterobacter spp., Staphylococcus spp, and E. faecalis.…”

Activity of Gatifloxacin in an In Vitro Pharmacokinetic-Pharmacodynamic Model against Staphylococcus aureus Strains either Susceptible to Ciprofloxacin or Exhibiting Various Levels and Mechanisms of Ciprofloxacin Resistance

“…Due to a high intrinsic activity (MIC, 0.1 g/ml), the concentration/MIC ratios of gatifloxacin reached 53 to 58 at the C max and were still 3 to 4 at the C res at 24 h. Since gatifloxacin is, like other quinolones, a zwitterion (pK a1 6.0 and pK a2 9.2) with an isoelectric point at pH 7.7, the degree of ionization is low in plasma (pH 7.4) (27). According to the principle of nonionic diffusion and to the low protein binding of fluoroquinolones, the highly vascularized tissue concentration of such a substance can be expected to approximate plasma levels such as those simulated in our model.…”

“…A 100-l volume from 17 PCp samples (0, 1,2,3,4,6,8,12, and 24 h after antibiotic administration for each regimen interval) was devoted to the bacterial growth quantification. For bacterial counts in the absence of antibiotic, a total of 17 samples were drawn from the PCp at 3,4,5,6,7,9,11,15,27,28,29,30,31,33,35,39, and 51 h after bacterial inoculation. Suspensions were 10-fold-diluted with a sterile 0.9% NaCl solution and plated on MH agar.…”