Prostatic penetration of meropenem in humans, and dosage considerations for prostatitis based on a site-specific pharmacokinetic/pharmacodynamic evaluation

The aims of this study were to investigate the penetration of meropenem (MER) into human prostate tissue and to assess MER regimens for prostatitis by performing a site-specific pharmacokinetic/pharmacodynamic evaluation. Patients with prostatic hypertrophy (n = 49) prophylactically received a 0.5-h infusion of MER (250 mg or 500 mg) before transurethral resection of the prostate. MER concentrations in plasma (0.5-5 h) and prostate tissue (0.5-1.5 h) were measured chromatographically. Concentration data were analysed pharmacokinetically with a three-compartment model and were used to estimate the drug exposure time above the minimum inhibitory concentration for bacteria (T > MIC, % of 24 h) in prostate tissue, an indicator for antibacterial effects at the site of action. The prostate tissue/plasma ratio was 16.6% for the maximum drug concentration and 17.7% for the area under the drug concentration-time curve, irrespective of the dose. Against MIC distributions for clinical isolates of Escherichia coli, Klebsiella spp. and Proteus spp., 500 mg once daily achieved a > 90% probability of attaining the bacteriostatic target (20% T > MIC) in prostate tissue, and 500 mg twice daily achieved a > 90% probability of attaining the bactericidal target (40% T > MIC) in prostate tissue. However, against the Pseudomonas aeruginosa isolates, none of the tested regimens achieved a > 90% probability of attaining the bacteriostatic or bactericidal targets. (C) 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.