Population Pharmacokinetics of a Novel Oral Fosfomycin Prophylactic Scheme in the Plasma and Prostate of Patients Undergoing Endoscopic Surgery for Benign Prostatic Hyperplasia

Sep 30, 2026

Population pharmacokinetics of an oral fosfomycin trometamol prophylactic scheme is developed for patients with benign prostatic hyperplasia undergoing endoscopic surgery. One- and two-compartment plasma models are fitted to fosfomycin plasma data, and plasma–prostate linked models are evaluated using nonlinear mixed-effects modelling. Monte Carlo simulations generate prostate concentration-time profiles and assess pharmacodynamic target attainment thresholds. The final approach uses two 3 g doses 12 h apart to support effective prostatic tissue concentrations during the post-scheme vulnerable period.

LanguageEnglish

CategoryHealthcare

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Pages10

Reading Time25 min

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Abstract

Background and Objective

Methods

Results

Conclusion

Key Points

Introduction

Clinical Pharmacokinetics (2026) 65:109–118 [https://doi.org/10.1007/s40262-025-01586-1](https://doi.org/10.1007/s40262-025-01586-1) Population Pharmacokinetics of a Novel Oral Fosfomycin Prophylactic Scheme in the Plasma and Prostate of Patients Undergoing Endoscopic Surgery for Benign Prostatic Hyperplasia Pier Giorgio Cojutti1,2 · Pasquale Maria Berrino3 · Valeria Rotaru3 · Lorenzo Bianchi3 · Riccardo Schiavina3 · Eugenio Brunocilla1,3 · Pierluigi Viale2,4 · Federico Pea1,2 Received: 3 May 2025 / Accepted: 1 October 2025 / Published online: 3 November 2025 © The Author(s) 2025 Abstract Background and Objective Fosfomycin trometamol may be a valuable option for antimicrobial prophylaxis before urological surgery for benign prostatic hyperplasia. The objective is to develop a population pharmacokinetic model of a novel oral fosfomycin prophylactic scheme in the plasma and prostate of patients undergoing endoscopic surgery for benign prostatic hyperplasia. Methods One-and two-compartment plasma pharmacokinetic models were fitted to fosfomycin plasma data, and different plasma-prostate linked models were tested by means of non-linear mixed effects modelling. Monte Carlo simulation was used to obtain 1000-subject concentration-time profiles of fosfomycin in the prostate. Probabilities of target attainment ≥ 90% of an area under the plasma concentration-time curve/minimum inhibitory concentration (MIC) > 83.3 and of a 70%t > MIC in the prostate were considered as optimal. Cumulative fractions of response against both wild-type and extended-spectrum beta-lactamase-producing Escherichia coli were calculated. Results A total of 104 patients, each providing a pair of plasma and prostate concomitant samples were included in the study. A one-compartment pharmacokinetic model was used to describe plasma fosfomycin concentration. Fosfomycin plasma– prostate relationships were adequately described by a direct response model with a power function. Simulations showed that fosfomycin disposition in the prostate was closely related to that in plasma. Optimal probabilities of target attainments were ensured against Enterobacterales having an MIC up to 0.5–1 mg/L in the 12 h vulnerable period after completing the prophylactic scheme. Conclusion A prophylactic regimen of two doses of oral fosfomycin trometamol 3 g 12 h apart before undergoing prostatic surgery may grant effective concentrations in the prostatic tissue of patients for a 12 h vulnerable period. 1 Introduction Benign prostatic hyperplasia is a common clinical condition associated with ageing [1] . At a population level, its prevalence is estimated to be as high as 70% in patients aged 60–69 years and higher than 80% in those aged over 70 years [2]. Benign prostatic hyperplasia may cause different lower urinary tract symptoms such as incomplete emptying, nocturia, weak stream, and frequency, sometimes urinary incontinence and in the most severe cases may be complicated by urinary tract infections (UTIs) [3] . Patients for whom medical therapy failed or was not tolerated are candidates for surgical intervention. Transurethral resection of the prostate Extended author information available on the last page of the article (TURP) has been the standard surgical procedure for decades. In most recent years, Holmium laser enucleation of the prostate (HoLEP) has been shown to be particularly advantageous for medical patients with complex case mix or for those with voluminous prostates [4–6] . TURP and HoLEP are clean-contaminated surgical procedures requiring antimicrobial prophylaxis . International guidelines recommend either trimethoprim/ sulfamethoxazole or an oral fluoroquinolone before intervention, essentially to counteract contamination by Enterobacterales, mainly by Escherichia coli [7 , 8] . Unfortunately, in the last two decades, the resistance rates of E. coli to these agents have continued to increase. Ina study including urinary tract E. coli isolate

FAQs

What was the study’s main objective?

To develop a population pharmacokinetic model for a novel oral fosfomycin prophylactic scheme in both plasma and prostate tissue of patients undergoing endoscopic surgery for benign prostatic hyperplasia.

How were pharmacokinetic models and simulations performed?

One- and two-compartment plasma models were fitted to plasma data, and plasma–prostate linked models were tested with nonlinear mixed-effects modelling. Monte Carlo simulations produced 1000-subject prostate concentration-time profiles.

Which prophylactic regimen does the study support?

A regimen of two doses of oral fosfomycin trometamol 3 g, given 12 hours apart before prostatic surgery, aimed at maintaining effective prostatic tissue concentrations for a 12-hour vulnerable period.

Sep 30, 2026

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