Penetration of Orally Administered Prulifloxacin into Human Prostate Tissue

Background and objective: Prulifloxacin, a fluoroquinolone antibacterial agent, may be a useful addition to the antimicrobial armamentarium against prostatitis once the ability of its active metabolite, ulifloxacin, to penetrate prostatic tissue has been determined. This study set out to evaluate ulifloxacin penetration into the prostate following administration of the oral fluoroquinolone prodrug prulifloxacin in patients undergoing transurethral resection of the prostate (TURP). Methods: This was a phase I, randomized, open-label, single-centre study involving 20 male Caucasian patients (mean age 63.1 years) requiring TURP for treatment of benign prostatic hyperplasia. Sixteen patients were randomized to receive prulifloxacin; the other four patients were not treated (controls) in order to validate the bioanalytical method. Patients in the active treatment groups were randomized to receive one or three once-daily doses of prulifloxacin 600 mg, with the last administration 3 hours prior to surgery. Central/transitional and peripheral zone prostatic tissue samples were obtained from the 6 o'clock and 9 o'clock positions in the prostate, and blood samples were collected concurrently. Ulifloxacin concentrations were determined in the tissue samples and plasma using liquid chromatography-tandem mass spectrometry. Safety was also assessed. Results: Prostatic tissue concentrations of ulifloxacin always exceeded those in plasma. Mean ulifloxacin concentrations measured in samples collected from the 6 o'clock central/transitional zone of the prostate were higher in patients who received prulifloxacin for 3 days than in those who received a single dose. Mean prostatic tissue/plasma ulifloxacin concentration ratios after single and repeated prulifloxacin administration ranged from 3.8 to 7.1 and from 3.9 to 9.5, respectively. The highest mean ratio was found in the 6 o'clock central/transitional zone after repeated dosing. Prostatic levels of ulifloxacin were above the minimum inhibitory concentrations for the most common causative pathogens of bacterial prostatitis. No treatment-related toxicities were reported. Conclusion: These findings confirm the ability of prulifloxacin to penetrate prostatic tissues, indicating high exposure of the target tissue to ulifloxacin and, therefore, a potential therapeutic role for prulifloxacin in the treatment of bacterial prostatic infections.