Estimating Unbound Drug Concentrations in Simulated Human Lung Fluid: Relevance to Lung Antibiotic PKPD

Estimating Unbound Drug Concentrations in Simulated Human Lung Fluid: Relevance to Lung Antibiotic PKPD

The use of unbound drug concentrations is crucial for the prediction of efficacious doses. Hence, dose predictions for antibiotics targeting respiratory pathogens should be based on free, rather than the currently used, total drug concentrations in epithelial lining fluid (ELF). In this work, we des...

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Veröffentlicht in:Molecular pharmaceutics 2023-07, Vol.20 (7), p.3578-3588
Hauptverfasser: Keemink, Janneke, Cantrill, Carina, Riboulet, William, Jurmanović, Stella, Pavlovski, Ivana, Bissantz, Caterina
Format: Artikel
Sprache:eng
Schlagworte:
Animals
Anti-Bacterial Agents - metabolism
Bronchoalveolar Lavage Fluid - chemistry
Humans
Lung - metabolism
Mice
Permeability
Pneumonia - metabolism
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Zusammenfassung:The use of unbound drug concentrations is crucial for the prediction of efficacious doses. Hence, dose predictions for antibiotics targeting respiratory pathogens should be based on free, rather than the currently used, total drug concentrations in epithelial lining fluid (ELF). In this work, we describe an assay to estimate the percent unbound of drugs in ELF using simulated epithelial lining fluid (sELF) containing the most abundant components of ELF in healthy humans. A diverse set of 85 compounds showed a broad range of unbound values ranging from
ISSN:1543-8384
1543-8392
DOI:10.1021/acs.molpharmaceut.3c00208