ArticleClinical pharmacokinetics2009
Defining the role of macrophages in local moxifloxacin tissue concentrations using biopsy data and whole-body physiologically based pharmacokinetic modelling.
Article in Clinical pharmacokinetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A Systematic Review of Published Models, Applications, and Model Verification.Drug metabolism and disposition: the biological fate of chemicals · 2015Pooled it
- PK/PD-Guided Strategies for Appropriate Antibiotic Use in the Era of Antimicrobial Resistance.Antibiotics (Basel, Switzerland) · 2025Review
- Physiologically based pharmacokinetic model combined with reverse dose method to study the nephrotoxic tolerance dose of tacrolimus.Archives of toxicology · 2023Article
- Development of a Minimalistic Physiologically Based Pharmacokinetic (mPBPK) Model for the Preclinical Development of Spectinamide Antibiotics.Pharmaceutics · 2023Article
- Mathematical model and tool to explore shorter multi-drug therapy options for active pulmonary tuberculosis.PLoS computational biology · 2020Article
- Targeting of Hepatic Macrophages by Therapeutic Nanoparticles.Frontiers in immunology · 2020Review
- Application of Physiologically-Based and Population Pharmacokinetic Modeling for Dose Finding and Confirmation During the Pediatric Development of Moxifloxacin.CPT: pharmacometrics & systems pharmacology · 2019Article
- Prediction of the pharmacokinetics and tissue distribution of levofloxacin in humans based on an extrapolated PBPK model.European journal of drug metabolism and pharmacokinetics · 2016Article
- Development of a Multicompartment Permeability-Limited Lung PBPK Model and Its Application in Predicting Pulmonary Pharmacokinetics of Antituberculosis Drugs.CPT: pharmacometrics & systems pharmacology · 2015Article
- Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2015Article
- A physiologically based pharmacokinetic model of rifampin in mice.Antimicrobial agents and chemotherapy · 2013Article
- Prediction of a potentially effective dose in humans for BAY 60-5521, a potent inhibitor of cholesteryl ester transfer protein (CETP) by allometric species scaling and combined pharmacodynamic and physiologically-based pharmacokinetic modelling.British journal of clinical pharmacology · 2012Article
- Cutting Edge PBPK Models and Analyses: Providing the Basis for Future Modeling Efforts and Bridges to Emerging Toxicology Paradigms.Journal of toxicology · 2012Article
- Translational PK/PD of anti-infective therapeutics.Drug discovery today. TechnologiesReview
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesThis study used a whole-body physiologically based pharmacokinetic (WB-PBPK) model for moxifloxacin, plus in vitro and in vivo literature data on its interaction with macrophages, to interpret biopsy results generated from patients undergoing primarily colorectal surgery.
methodsA WB-PBPK model was developed using PK-Sim(R) software and refined using observed plasma profiles. The model was assessed by comparing predictions of unbound interstitial concentrations with in vivo data from a microdialysis study.
resultsIncorporating in vitro data on the percentage volume of macrophages in a colorectal resection (8.1%) plus the in vivo kinetic and accumulation potential of moxifloxacin in macrophages into the WB-PBPK model, biopsy concentrations and kinetics were predicted and compared with observed data. The WB-PBPK model accurately described adipose and muscle interstitial unbound concentrations. The predicted biopsy concentrations (including interstitial, intracellular, vascular space and macrophages) were slightly greater than the observed values, although the kinetic (i.e. observed biopsy half-life = 21 hours) was similar to that of moxifloxacin in macrophages (20.8 hours) and thus similar to the predicted biopsy half-life. A reduction in the predicted biopsy concentrations to match the observed data required a decrease in the volume fraction of macrophages from 8.1% to 3.6%.
conclusionWhen plasma concentrations are known, WB-PBPK is a method to determine interstitial and intracellular concentrations. In this study, integration of biopsy data with WB-PBPK allowed for generation and testing of hypotheses to determine the reason for the observed biopsy kinetics. This type of translational modelling may lead to a better understanding of the anti-infective pharmacokinetic/pharmacodynamic relationship.
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