Predicting systemic and pulmonary tissue barrier concentration of orally inhaled drug products
Abstract
Abstract The complex physiology and anatomy of the lungs and the range of processes involved in pulmonary drug transport and disposition make it challenging to predict the fate of orally inhaled drugs. This study aimed to develop an integrated computational pharmacology approach to mechanistically describe the spatio-temporal dynamics of inhaled drugs in both systemic circulation and site-specific lung tissue. The model included all the physiologically relevant pulmonary processes, such as deposition, dissolution, transport across lung barriers, and mucociliary clearance, to predict the inhaled drug pharmacokinetics. For validation test cases, the model predicted the fate of orally inhaled budesonide (highly soluble, mildly lipophilic) and fluticasone propionate (practically insoluble, highly lipophilic) in healthy subjects for: i) systemic and site-specific lung retention profiles, ii) aerodynamic particle size-dependent deposition profiles, and iii) identified the most impactful drug-specific, formulation-specific, and system-specific property factors that impact the fate of both the pulmonary and systemic concentration of the drugs. In summary, the presented multiscale computational model can guide the design of orally inhaled drug products to target specific lung areas, identify the effects of product differences on lung and systemic pharmacokinetics, and be used to better understand bioequivalence of generic orally inhaled drug products. Author summary Despite…
Read the paper
Related studies
- Global, regional, and national burden of hepatitis B, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019
- A meta‐analysis of anal cancer incidence by risk group: Toward a unified anal cancer risk scale
- Global fertility in 204 countries and territories, 1950–2021, with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021
- Exercise interventions in Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials
- Prognostic Significance of Carbonic Anhydrase IX Expression in Cancer Patients: A Meta-Analysis
- Glucocorticoid Resistance: Is It a Requisite for Increased Cytokine Production in Depression? A Systematic Review and Meta-Analysis
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.