title: Prostatic penetration of meropenem in humans, and dosage considerations for prostatitis based on a site-specific pharmacokinetic/pharmacodynamic evaluation.
abstract: 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 (0.5-5h) and prostate tissue (0.5-1.5h) 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 24h) 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.
authors: Department of Urology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan. genchari@aichi-med-u.ac.jp
authors: Genya
authors: G
authors: Nishikawa
authors: Kazuro
authors: K
authors: Ikawa
authors: Kogenta
authors: K
authors: Nakamura
authors: Yoshiaki
authors: Y
authors: Yamada
authors: Kenji
authors: K
authors: Zennami
authors: Kenji
authors: K
authors: Mitsui
authors: Masahiro
authors: M
authors: Narushima
authors: Kayo
authors: K
authors: Ikeda
authors: Norifumi
authors: N
authors: Morikawa
authors: Makoto
authors: M
authors: Sumitomo
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002845:Chromatography; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D010949:Plasma / Q000737:chemistry; D011467:Prostate / Q000737:chemistry*; D011472:Prostatitis / Q000188:drug therapy*; D013845:Thienamycins / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem