Inhalation Toxicology*

Hoffman, Gary S.; Cracknell, Stuart; Damiano, Justine; Macri, Nicholas P.; Moore, Simon

doi:10.1201/b16632-7

Cited by 1 publication

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“…The thickness of the lining fluid layer was reported as 5–10 μm in the conducting airways and 0.01–0.08 μm in the alveoli (Olsson et al, 2011 ). Other data report a 10–30 μm thick layer in the trachea, 2–5 μm in the bronchi, and 0.1–0.2 μm in the alveoli (Wauthoz and Amighi, 2015 ), 10 μm in the upper airways, 3–5 μm in the alveolar ducts and 0.3 μm in the alveoli (National Research Council, 1977 ) or 8.3–6.9 μm in bronchi and 1.8 μm in bronchioles (Hoffmann et al, 2014 ). Patton and Byron reported 8 μm for bronchi, 3 μm for terminal bronchioles and 0.07 μm for alveoli (Patton and Byron, 2007 ).…”

Section: Distribution Volume and Protein Contentmentioning

confidence: 99%

Measurements of Deposition, Lung Surface Area and Lung Fluid for Simulation of Inhaled Compounds

et al. 2016

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Modern strategies in drug development employ in silico techniques in the design of compounds as well as estimations of pharmacokinetics, pharmacodynamics and toxicity parameters. The quality of the results depends on software algorithm, data library and input data. Compared to simulations of absorption, distribution, metabolism, excretion, and toxicity of oral drug compounds, relatively few studies report predictions of pharmacokinetics and pharmacodynamics of inhaled substances. For calculation of the drug concentration at the absorption site, the pulmonary epithelium, physiological parameters such as lung surface and distribution volume (lung lining fluid) have to be known. These parameters can only be determined by invasive techniques and by postmortem studies. Very different values have been reported in the literature. This review addresses the state of software programs for simulation of orally inhaled substances and focuses on problems in the determination of particle deposition, lung surface and of lung lining fluid. The different surface areas for deposition and for drug absorption are difficult to include directly into the simulations. As drug levels are influenced by multiple parameters the role of single parameters in the simulations cannot be identified easily.

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