Determination of doripenem penetration into human prostate tissue and assessment of dosing regimens for prostatitis based on site-specific pharmacokinetic-pharmacodynamic evaluation

作者：Nakamura Kogenta^*; Ikawa Kazuro; Yamada Yoshiaki; Arakawa Maki; Zennami Kenji; Nishikawa Genya; Ikeda Kayo; Morikawa Norifumi; Honda Nobuaki

来源：Journal of Chemotherapy, 2012, 24(1): 32-37.

DOI：10.1179/1120009X12Z.0000000007

• Doripenem
• Prostate tissue
• Prostatitis
• PK-PD
• Transurethral resection of the prostate

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%26gt;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 %26gt;90% probability of attaining the bacteriostatic target (20% T%26gt;MIC) in prostate tissue, and 500 mg twice daily achieved a %26gt;90% probability of attaining the bactericidal target (40% T%26gt;MIC) in prostate tissue.

• 出版日期2012-2