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.
Yamada
Yoshiaki
Y
Department of Urology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
Ikawa
Kazuro
K
Nakamura
Kogenta
K
Mitsui
Kenji
K
Narushima
Masahiro
M
Hibi
Hatsuki
H
Ikeda
Kayo
K
Morikawa
Norifumi
N
Honda
Nobuaki
N
D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D015780:Carbapenems / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002845:Chromatography; D000077726:Doripenem; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000737:chemistry*; D011468:Prostatectomy; D044967:Serum / Q000737:chemistry
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000077726:Doripenem