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

Kogenta Nakamura, Kazuro Ikawa, Yoshiaki Yamada, Maki Arakawa, Kenji Zennami, Genya Nishikawa, Kayo Ikeda, Norifumi Morikawa, Nobuaki Honda

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)32-37
Number of pages6
JournalJournal of Chemotherapy
Volume24
Issue number1
DOIs
Publication statusPublished - 01-02-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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