Clinical pharmacokinetics and pharmacodynamic target attainment of pazufloxacin in prostate tissue: Dosing considerations for prostatitis.

The present study examined the clinical pharmacokinetics of pazufloxacin in prostate tissue and estimated the probability of target attainment for tissue-specific pharmacodynamic goals related to treating prostatitis using various intravenous dosing regimens. Patients with prostatic hypertrophy received prophylactic infusions of pazufloxacin (500 mg, n = 23; 1000 mg, n = 25) for 0.5 h prior to transurethral prostate resection. Drug concentrations in plasma (0.5-5 h) and prostate tissue (0.5-1.5 h) were measured by high-performance liquid chromatography and used for subsequent noncompartmental and three-compartmental analysis. Monte Carlo simulation was performed to evaluate the probability of target attainment of a specific minimum inhibitory concentration (MIC) in prostate tissue: the proportion that achieved both area under the drug concentration over time curve (AUC)/MIC = 100 and maximum concentration (Cmax)/MIC = 8. Prostatic penetration of pazufloxacin was good with mean Cmax ratios (prostate tissue/plasma) of 0.82-0.99 and for AUC, 0.80-0.98. The probability of reaching target MIC concentrations in prostate tissue was more than 90% for dosing schedules of 0.25 mg/L for 500 mg every 24 h (500 mg daily), 0.5 mg/L for 500 mg every 12 h (1000 mg daily), 1 mg/L for 1000 mg every 24 h (1000 mg daily), and 2 mg/L for 1000 mg every 12 h (2000 mg daily). Importantly, the 2000 mg daily regimen of pazufloxacin produced a profile sufficient to have an antibacterial effect in prostate tissue against clinical isolates of Escherichia coli and Klebsiella pneumonia with MIC values less than 2 mg/L.

Penetration of piperacillin-tazobactam into human prostate tissue and dosing considerations for prostatitis based on site-specific pharmacokinetics and pharmacodynamics.

This study aimed to investigate the penetration of PIPC-TAZ into human prostate, and to assess effectiveness of PIPC-TAZ against prostatitis by evaluating site-specific PK-PD. Patients with prostatic hypertrophy (n = 47) prophylactically received a 0.5 h infusion of PIPC-TAZ (8:1.2-0.25 g or 4-0.5 g) before transurethral resection of the prostate. PIPC-TAZ concentrations in plasma (0.5-5 h) and prostate tissue (0.5-1.5 h) were analyzed with a three-compartment PK model. The estimated model parameters were, then used to estimate the drug exposure time above the minimum inhibitory concentration for bacteria (T > MIC, the PD indicator for antibacterial effects) in prostate tissue for six PIPC-TAZ regimens (2.25 or 4.5 g; once, twice, three times or four times daily; 0.5 h infusions). Prostate tissue/plasma ratio of PIPC was about 36% both for the maximum drug concentration (Cmax) and the area under the drug concentration-time curve (AUC). Against MIC distributions for isolates of Escherichia coli, Klebsiella species and Proteus species, regimens of 4.5 g twice daily and 2.25 g three times daily achieved a >90% probability of attaining the bacteriostatic target for PIPC (30% T > MIC) in prostate tissue; regimens of 4.5 g three times daily and 2.25 g four times daily achieved a >90% probability of attaining the bactericidal target for PIPC (50% T > MIC) in prostate tissue. However, against Pseudomonas aeruginosa isolates, none of the tested regimens achieved a >90% probability. PIPC-TAZ is appropriate for the treatment of prostatitis from the site-specific PK-PD perspective.