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

This study examined the prostatic penetration of doripenem in prostatectomy patients. Doripenem 500 mg 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+/-5.1 microg/mL in plasma and 5.09+/-1.94 microg/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+/-6.9 microg h/mL in plasma and 3.93+/-1.89 microg h/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 0.25 microg/mL (the minimum inhibitory concentration for isolates of common pathogens) in the prostate were 23.2% for 500 mg once daily, 46.2% for 500 mg twice daily and 69.9% for 500 mg 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.