Prostatic Pharmacokinetic and Pharmacodynamic Analysis of Ceftazidime: Dosing Strategy for Bacterial Prostatitis

• Published in: Journal of clinical pharmacology
• Main Authors: Onita, Tetsushu, Nakamura, Kogenta, Nishikawa, Genya, Ishihara, Noriyuki, Tamaki, Hiroki, Yano, Takahisa, Naora, Kohji, Morikawa, Norifumi, Ikawa, Kazuro
• Format: Journal Article
• Language: English
• Published: England 01.01.2025
• Subjects: modeling and simulation; pharmacokinetics; bacterial prostatitis; ceftazidime; pharmacodynamics
• ISSN: 1552-4604
• DOI: 10.1002/jcph.6119

This study aimed to develop a prostatic pharmacokinetic model of ceftazidime and suggest more effective dosing strategy for the bacterial prostatitis, based on a site-specific pharmacokinetic and pharmacodynamic perspective. Subjects were prostatic hyperplasia patients prophylactically receiving a 0.5-h infusion of 1.0 g or 2.0 g ceftazidime before transurethral resection of the prostate. Plasma and prostate samples were premeditatedly collected after the administration and the concentrations were measured by high-performance liquid chromatography. The prostate tissue/plasma ratio in area under the drug concentration-time curve was approximately 0.476. The prostatic population pharmacokinetic model incorporated creatinine clearance (CL ) into ceftazidime clearance was developed, and adequately predicted prostate tissue concentrations by diagnostic scatter plots and visual predictive checks. Aiming for a bactericidal target of 70% of time above minimum inhibitory concentration (T > MIC) in prostate tissue, 2.0 g twice daily achieved ≥90% expected probability against main pathogens like Escherichia coli and Proteus species in patients regardless of renal function (CL = 60 and 90 mL/min). However, since the expected probability of attaining the bactericidal target of 0.5-h infusion dosing regimen did not achieve 90% against Pseudomonas aeruginosa in patients with CL = 60 and 90 mL/min, 4-h infusion dosing regimen of 2.0 g three times daily (6 g/day) might be required for empirical treatment. Based on site-specific simulations, the present study provides more effective dosing strategy for bacterial prostatitis.