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

Abstract

AbstractThis 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 (CLcr) 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 (CLcr = 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 CLcr = 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.