<b>Integration of Computational Fluid Dynamics and Physiologically Based Pharmacokinetic Modeling to Predict Human Pulmonary Absorption and Systemic Exposure of Inhaled Drugs</b>

We developed an integrated computational fluid dynamics (CFD)-PBPK framework that links generation-resolved particle deposition with mechanistic pulmonary absorption to predict human PK using <i>in vitro</i> and<i> </i><i>in silico</i> inputs.

Airflow-driven particle deposition across airway generations 0-23 was characterized using a two-dimensional CFD model, wherein a particle size-dependent deposition velocity () was introduced and calculated based on particle diameter. Generation-specific deposited doses estimated from aerosol properties provided the initial conditions for subsequent PBPK simulations. Dissolution, epithelial permeation, and mucociliary clearance were parameterized from commonly measured<i> </i><i>in vitro</i>/<i>in silico</i> data, while systemic disposition was described by a minimal PBPK model fitted to intravenous PK data.