Prostatic Pharmacokinetic/Pharmacodynamic Evaluation of Ampicillin-Sulbactam for Bacterial Prostatitis and Preoperative Prophylaxis.

Tetsushu Onita, Kazuro Ikawa, Kogenta Nakamura, Genya Nishikawa, Ikuo Kobayashi, Noriyuki Ishihara, Hiroki Tamaki, Takahisa Yano, Kohji Naora, Norifumi Morikawa

Journal of clinical pharmacology 2021 Jun

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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 (CLcr ) 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 CLcr 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. © 2020, The American College of Clinical Pharmacology.

Citation

Tetsushu Onita, Kazuro Ikawa, Kogenta Nakamura, Genya Nishikawa, Ikuo Kobayashi, Noriyuki Ishihara, Hiroki Tamaki, Takahisa Yano, Kohji Naora, Norifumi Morikawa. Prostatic Pharmacokinetic/Pharmacodynamic Evaluation of Ampicillin-Sulbactam for Bacterial Prostatitis and Preoperative Prophylaxis. Journal of clinical pharmacology. 2021 Jun;61(6):820-831