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Updated: Jul 9, 2026

Longitudinal Follow-Up of Urinary Tract Infections and Their Treatment in Mice using Bioluminescence Imaging
07:39

Longitudinal Follow-Up of Urinary Tract Infections and Their Treatment in Mice using Bioluminescence Imaging

Published on: June 14, 2021

Flucloxacillin plasma and urinary concentrations with and without probenecid and urinary biomarker profiles in

Amy Legg1,2,3, Alison Boast4,5,6, Kim Piera1

  • 1Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.

British Journal of Clinical Pharmacology
|July 7, 2026
PubMed
Abstract

Insights

Probenecid significantly increases flucloxacillin levels, improving treatment effectiveness for Staphylococcus aureus infections. This combination allows for less frequent dosing, potentially enhancing patient adherence and outcomes.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Clinical Pharmacy

Background:

  • Oral flucloxacillin is a common treatment for methicillin-susceptible Staphylococcus aureus (MSSA) infections.
  • Current 6-hourly dosing regimens may pose challenges for patient adherence.
  • Probenecid is known to inhibit renal excretion of beta-lactam antibiotics, increasing drug exposure.

Purpose of the Study:

  • To investigate the impact of probenecid on flucloxacillin pharmacokinetics and pharmacodynamics.
  • To assess the effect of probenecid on serum and urinary flucloxacillin concentrations.
  • To evaluate the potential for less frequent flucloxacillin dosing when co-administered with probenecid.

Main Methods:

  • Ten healthy adults received intravenous and oral flucloxacillin, with and without probenecid.
  • Pharmacokinetic analysis using UHPLC-MS/MS and population modeling.
  • Monte Carlo simulations to determine probability of target attainment (PTA).
  • Monitoring of urinary biomarkers and renal function.

Main Results:

  • Probenecid significantly increased unbound flucloxacillin concentrations (0.74 vs 0.30 mg/L) and reduced clearance (46.9 vs 143 L/h).
  • Simulations indicated improved PTA with probenecid (84% for 8-hourly dosing) versus standard dosing alone (6%).
  • No serious adverse events were reported; renal function markers remained stable.

Conclusions:

  • Co-administration of probenecid substantially enhances flucloxacillin exposure.
  • This combination demonstrates potential for optimizing dosing strategies for MSSA infections.
  • Further clinical trials are warranted to validate these findings in infected patients.
Keywords:
flucloxacillinpharmacodynamicspharmacokineticsprobenecidstaphylococcal infections

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