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Prostatic Pharmacokinetic/Pharmacodynamic Evaluation of Ampicillin‐Sulbactam for Bacterial Prostatitis and Preoperative Prophylaxis
Author(s) -
Onita Tetsushu,
Ikawa Kazuro,
Nakamura Kogenta,
Nishikawa Genya,
Kobayashi Ikuo,
Ishihara Noriyuki,
Tamaki Hiroki,
Yano Takahisa,
Naora Kohji,
Morikawa Norifumi
Publication year - 2021
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.1800
Subject(s) - medicine , sulbactam , pharmacokinetics , urology , prostate , prostatitis , pharmacodynamics , ampicillin , population , prostatectomy , physiologically based pharmacokinetic modelling , pharmacology , antibiotics , biology , antibiotic resistance , microbiology and biotechnology , environmental health , imipenem , cancer
This study aims to define the penetration of ampicillin and sulbactam into prostate tissue, develop a prostatic pharmacokinetic model of each drug, and assess the appropriateness of ampicillin‐sulbactam regimens for the treatment of prostatitis and the prophylaxis of postoperative infection, based on a pharmacokinetic and pharmacodynamic simulation. Subjects were prostatic hyperplasia patients prophylactically receiving a 0.5‐hour infusion of 1.5 g (1:0.5 g) or 3 g (2:1 g) ampicillin‐sulbactam before transurethral resection of the prostate. Ampicillin and sulbactam concentrations in plasma and prostate tissue were measured. The prostate tissue/plasma ratios of both ampicillin and sulbactam were approximately 0.37 (area under the drug concentration‐time curve), and penetration was similar. The prostatic population pharmacokinetic model, which included a covariate analysis, adequately predicted prostate tissue concentrations in our patient population. For therapeutic use, aiming for a bactericidal target of 50% of time above minimum inhibitory concentration (T > MIC) in prostate tissue, 3 g ampicillin‐sulbactam 4 times daily achieved ≥90% expected probability against only Enterococcus faecalis in typical patients with a creatinine clearance (CL cr ) of 30 mL/min. For prophylactic use, aiming for a bacteriostatic target of 30% T > MIC, 3 g ampicillin‐sulbactam 4 times daily achieved ≥90% expected probability of attaining the bacteriostatic target against E. faecalis and Proteus species when CL cr was 30 mL/min. Based on prostatic simulations, the present study provides helpful recommendations for the treatment of bacterial prostatitis and preoperative prophylaxis in prostatectomy.