Insights into amoxicillin pharmacokinetics using physiology-based pharmacokinetic modelling
Christopher A Darlow1, Vineet Dubey1, Nada Reza1
1Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool, United Kingdom.
Antimicrobial Agents and Chemotherapy
|July 17, 2026
Summary
A new physiology-based pharmacokinetic (PBPK) model for amoxicillin reveals treatment adequacy for common bacterial infections. The model also highlights the impact of missed doses and drug interactions on amoxicillin effectiveness.
Area of Science:
- Pharmacology
- Microbiology
- Computational Biology
Background:
- Amoxicillin is a widely used antibiotic with limited understanding of its pharmacokinetic and pharmacodynamic properties.
- Optimizing amoxicillin dosing is crucial for treating global health infections effectively.
Purpose of the Study:
- To develop a physiology-based pharmacokinetic (PBPK) model for amoxicillin.
- To assess the adequacy of amoxicillin regimens for common bacterial infections using the PBPK model.
Main Methods:
- Constructed an amoxicillin PBPK model in PK-Sim using ADME and physicochemical parameters, in vitro transporter kinetics (OAT3), and published time-concentration data.
- Fitted unknown parameters using clinical pharmacokinetic data for training and validated the model with a holdout dataset.
- Performed population simulations for various amoxicillin regimens and contexts.
Main Results:
- The amoxicillin PBPK model demonstrated high performance in predicting plasma and urinary concentrations.
- Simulations indicated that most amoxicillin regimens achieve the target 40%T>MIC for Streptococcus pneumoniae and Haemophilus influenzae.
- The model evaluated the impact of factors like missed doses, reduced active ingredient content, and probenecid co-administration on antimicrobial coverage, revealing high urinary amoxicillin exposure.
Conclusions:
- The developed PBPK model provides valuable insights into amoxicillin pharmacokinetics and treatment efficacy.
- It confirms the adequacy of amoxicillin for S. pneumoniae and H. influenzae infections under various conditions.
- The model underscores the importance of adherence, active ingredient integrity, and potential benefits of probenecid, while noting high urinary concentrations relevant for urinary tract infections.
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