Development of a Novel Multi-compartment Granuloma Model to Predict Local Drug Distribution and Its Impact on Pharmacodynamics and Disease Progression in Tuberculosis

Objectives: One of the hallmarks of pulmonary tuberculosis (TB) is the formation of granulomas, heterogeneous lesions composed of macrophage and neutrophil rich peripheral regions and a necrotic core, in the lungs of the infected host. Anti-TB drugs must penetrate these lesions to exert their effects. This work aimed to extend a permeability-limited lung model [1] […]

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Development of a Multicompartment Permeability-Limited Lung PBPK Model and Its Application in Predicting Pulmonary Pharmacokinetics of Antituberculosis Drugs

Achieving sufficient concentrations of antituberculosis (TB) drugs in pulmonary tissue at the optimum time is still a challenge in developing therapeutic regimens for TB. A physiologically based pharmacokinetic model incorporating a multi-compartment permeability-limited lung model was developed and used to simulate plasma and pulmonary concentrations of seven drugs. Passive permeability of drugs within the lung was predicted using an in vitro-in vivo extrapolation approach. Simulated epithelial lining fluid (ELF):plasma concentration ratios showed reasonable […]

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