title: Determination of doripenem penetration into human prostate tissue and assessment of dosing regimens for prostatitis based on site-specific pharmacokinetic-pharmacodynamic evaluation.
abstract: Prostatic hypertrophy patients prophylactically received a 0.5-hour infusion of doripenem (250 or 500 mg) before transurethral resection of the prostate. Doripenem concentrations in plasma and prostate tissue were measured chromatographically, and analysed pharmacokinetically using a three-compartment model. The approved doripenem regimens were assessed based on the time above the minimum inhibitory concentration for bacteria (T>MIC, % of 24 hours), an indicator for antibacterial effects, at the prostate. The prostate tissue/plasma ratios were 17.3% for the maximum drug concentration and 18.7% for the area under the drug concentration-time curve, and they were irrespective of the dose. Against Escherichia coli and Klebsiella species isolates, 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.
authors.affiliation: Department of Urology, Aichi Medical University School of Medicine, Aichi, Japan. kogenaka@aichi-med-u.ac.jp
authors.forename: Kogenta
authors.initials: K
authors.lastname: Nakamura
authors.forename: Kazuro
authors.initials: K
authors.lastname: Ikawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamada
authors.forename: Maki
authors.initials: M
authors.lastname: Arakawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Zennami
authors.forename: Genya
authors.initials: G
authors.lastname: Nishikawa
authors.forename: Kayo
authors.initials: K
authors.lastname: Ikeda
authors.forename: Norifumi
authors.initials: N
authors.lastname: Morikawa
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Honda
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D015780:Carbapenems / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D003198:Computer Simulation; D000077726:Doripenem; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D011467:Prostate / Q000187:drug effects*; D011472:Prostatitis / Q000188:drug therapy*; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000077726:Doripenem