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.

Keywords:

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

The authors thank all investigators who contributed to this study.