Penetration of piperacillin–tazobactam into human prostate tissue and dosing considerations for prostatitis based on site-specific pharmacokinetics and pharmacodynamics. Issue 8 (August 2015)

• Record Type: Journal Article
• Authors: Kobayashi, Ikuo; Ikawa, Kazuro; Nakamura, Kogenta; Nishikawa, Genya; Kajikawa, Keishi; Yoshizawa, Takahiko; Watanabe, Masahito; Kato, Yoshiharu; Zennami, Kenji; Kanao, Kent; Tobiume, Motoi; Yamada, Yoshiaki; Mitsui, Kenji; Narushima, Masahiro; Morikawa, Norifumi; Sumitomo, Makoto
• Is Part Of: Journal of infection and chemotherapy. Volume 21:Issue 8(2015:Aug.)
• Page Start: 575
• Page End: 580
• Publication Date: 2015-08
• Subjects: Chemotherapy -- Periodicals; Infection -- Periodicals; Communicable diseases -- Chemotherapy -- Periodicals; 615.5805
• DOI: 10.1016/j.jiac.2015.04.015
• Languages: English
• ISSNs: 1341-321X

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Abstract</title> <sec> <p id="abspara0010">This study aimed to investigate the penetration of PIPC–TAZ into human prostate, and to assess effectiveness of PIPC–TAZ against prostatitis by evaluating site-specific PK–PD. Patients with prostatic hypertrophy (<italic>n</italic> = 47) prophylactically received a 0.5 h infusion of PIPC–TAZ (8:1.2–0.25 g or 4–0.5 g) before transurethral resection of the prostate. PIPC–TAZ concentrations in plasma (0.5–5 h) and prostate tissue (0.5–1.5 h) were analyzed with a three-compartment PK model. The estimated model parameters were, then used to estimate the drug exposure time above the minimum inhibitory concentration for bacteria (<italic>T</italic> > MIC, the PD indicator for antibacterial effects) in prostate tissue for six PIPC–TAZ regimens (2.25 or 4.5 g; once, twice, three times or four times daily; 0.5 h infusions). Prostate tissue/plasma ratio of PIPC was about 36% both for the maximum drug concentration (<italic>C</italic><sub>max</sub>) and the area under the drug concentration–time curve (AUC). Against MIC distributions for isolates of <italic>Escherichia coli</italic>, <italic>Klebsiella</italic> species and <italic>Proteus</italic> species, regimens of 4.5 g twice daily and 2.25 g three times daily achieved a >90% probability of attaining the bacteriostatic target for PIPC (30% <italic>T</italic> > MIC) in prostate tissue; regimens of 4.5 g three times daily and 2.25 g four times daily achieved a >90% probability of attaining the bactericidal target for PIPC (50% <italic>T</italic> > MIC) in prostate tissue. However, against <italic>Pseudomonas aeruginosa</italic> isolates, none of the tested regimens achieved a >90% probability. PIPC–TAZ is appropriate for the treatment of prostatitis from the site-specific PK–PD perspective.</p> </sec> </abstract>