ArticleClinical pharmacokinetics2017
Development of a Physiologically Based Pharmacokinetic Modelling Approach to Predict the Pharmacokinetics of Vancomycin in Critically Ill Septic Patients.
Article in Clinical pharmacokinetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Transporter-Drive Interstitial Tissue Exposure and Pharmacodynamic Response of Meropenem in Sepsis: A Mechanistic PBPK Modeling Study.CPT: pharmacometrics & systems pharmacology · 2026Article
- Integrating CRRT as a Virtual Organ Into Physiologically Based Pharmacokinetic Modeling to Optimize Antimicrobial Dosing in Septic Patients.CPT: pharmacometrics & systems pharmacology · 2026Article
- A Review of Virtual Twins in Physiologically-Based Pharmacokinetic Modeling and Simulation.Clinical pharmacology and therapeutics · 2026Review
- From Population-Based PBPK to Individualized Virtual Twins: Clinical Validation and Applications in Medicine.Journal of clinical medicine · 2026Review
- Assessment of Vancomycin Penetration into Cerebrospinal Fluid in Patients with Ventriculitis Using a Physiologically Based Pharmacokinetic Approach.Pharmaceutical research · 2026Article
- Physiologically-based pharmacokinetic model to predict loading dose polymyxin B exposure in critically ill patients with sepsis.Frontiers in pharmacology · 2026Article
- PBPK/PD Model of Vancomycin in Sepsis: Linking Interstitial Exposure in Perfusion-Limited Tissues to MRSA Infection.Pharmaceutics · 2025Article
- Physiologically Based Pharmacokinetic Model of Cefotaxime in Patients with Impaired Renal Function.Clinical pharmacokinetics · 2025Article
- PK/PD-Guided Strategies for Appropriate Antibiotic Use in the Era of Antimicrobial Resistance.Antibiotics (Basel, Switzerland) · 2025Review
- Utilizing Physiologically Based Pharmacokinetic Models to Support Rational Medication in Chinese Elderly Population.Drug design, development and therapy · 2025Article
- Physiologically Based Pharmacokinetic Modelling in Critically Ill Children Receiving Anakinra While on Extracorporeal Life Support.Clinical pharmacokinetics · 2024Article
- Advancing personalized medicine for tuberculosis through the application of immune profiling.Frontiers in cellular and infection microbiology · 2023Review
- Feasibility of a Pragmatic PBPK Modeling Approach: Towards Model-Informed Dosing in Pediatric Clinical Care.Clinical pharmacokinetics · 2022Article
- The Issue of Pharmacokinetic-Driven Drug-Drug Interactions of Antibiotics: A Narrative Review.Antibiotics (Basel, Switzerland) · 2022Review
- Prediction of cytochromes P450 3A and 2C19 modulation by both inflammation and drug interactions using physiologically based pharmacokinetics.CPT: pharmacometrics & systems pharmacology · 2022Article
- Pharmacokinetic assessment of vancomycin in critically ill patients and nephrotoxicity prediction using individualized pharmacokinetic parameters.Frontiers in pharmacology · 2022Article
- Biomarker-Guided Individualization of Antibiotic Therapy.Clinical pharmacology and therapeutics · 2021Review
- Development of a physiologically based pharmacokinetic (PBPK) population model for Chinese elderly subjects.British journal of clinical pharmacology · 2021Article
- Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature.Frontiers in pharmacology · 2021Review
- Comparing Predictions of a PBPK Model for Cyclosporine With Drug Levels From Therapeutic Drug Monitoring.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesSepsis is characterised by an excessive release of inflammatory mediators substantially affecting body composition and physiology, which can be further affected by intensive care management. Consequently, drug pharmacokinetics can be substantially altered. This study aimed to extend a whole-body physiologically based pharmacokinetic (PBPK) model for healthy adults based on disease-related physiological changes of critically ill septic patients and to evaluate the accuracy of this PBPK model using vancomycin as a clinically relevant drug.
methodsThe literature was searched for relevant information on physiological changes in critically ill patients with sepsis, severe sepsis and septic shock. Consolidated information was incorporated into a validated PBPK vancomycin model for healthy adults. In addition, the model was further individualised based on patient data from a study including ten septic patients treated with intravenous vancomycin. Models were evaluated comparing predicted concentrations with observed patient concentration-time data.
resultsThe literature-based PBPK model correctly predicted pharmacokinetic changes and observed plasma concentrations especially for the distribution phase as a result of a consideration of interstitial water accumulation. Incorporation of disease-related changes improved the model prediction from 55 to 88% within a threshold of 30% variability of predicted vs. observed concentrations. In particular, the consideration of individualised creatinine clearance data, which were highly variable in this patient population, had an influence on model performance.
conclusionPBPK modelling incorporating literature data and individual patient data is able to correctly predict vancomycin pharmacokinetics in septic patients. This study therefore provides essential key parameters for further development of PBPK models and dose optimisation strategies in critically ill patients with sepsis.
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