Penetration of doripenem into prostatic tissue following intravenous administration in prostatectomy patients

Abstract 

This study examined the prostatic penetration of doripenem in prostatectomy patients. Doripenem 500mg was administered by a 0.5-h infusion and venous blood and prostatic tissue samples were obtained up to 5h afterwards. Drug concentrations in plasma and prostatic tissue were measured chromatographically. The observed maximum concentration (C_max) (mean±standard deviation; n=9) was 27.5±5.1μg/mL in plasma and 5.09±1.94μg/g in prostate tissue and the prostate/plasma C_max ratio was 0.189±0.078. The area under the drug concentration–time curve (AUC) was 49.7±6.9μgh/mL in plasma and 3.93±1.89μgh/g in prostate tissue and the prostate/plasma AUC ratio was 0.081±0.047. Based on a three-compartment pharmacokinetic analysis, average drug exposure times above 0.25μg/mL (the minimum inhibitory concentration for isolates of common pathogens) in the prostate were 23.2% for 500mg once daily, 46.2% for 500mg twice daily and 69.9% for 500mg three times daily. The 500-mg regimens all achieved the drug exposure time target (bacteriostatic 20% or bactericidal 40%) in the prostate, despite the relatively low penetrability of doripenem.

Keywords: Carbapenem, Pharmacokinetics, Bacterial prostatitis