Translational Physiologically Based Pharmacokinetic Modeling to Predict Human Pulmonary Kinetics After Lung Delivery.

ABSTRACT: Predicting human lung exposure with reasonable certainty of orally inhaled drugs based on preclinical studies remains a challenge for drug development. We have developed a comprehensive physiologically based pharmacokinetic (PBPK) framework tailored for the pulmonary pharmacokinetic (PK) behavior in both humans and rats, aiming to bridge the translational gap. In this study, we present a mechanistic pulmonary PBPK model for rats that integrates the pulmonary disposition processes, including drug deposition, dissolution, mucociliary clearance, and mass transfer in lung tissues. Apparent permeabilities were translated to effective permeabilities (P_eff) with in vivo-in vitro correlation methods. Unbound tissue-plasma partition coefficients for lung (K_p,u,lung) and P

SUBMITTER: Wen H 

PROVIDER: S-EPMC12001274 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature