Background

Pulmonary drug delivery via inhalation offers significant clinical benefits including rapid onset of action and targeted drug administration, which minimizes systemic adverse effects. Despite these advantages, the anatomical and physiological complexity of the lungs, together with the physicochemical characteristics of inhaled agents and formulation variables, presents considerable difficulties for reliably predicting drug deposition, dissolution, absorption, and systemic pharmacokinetics (PKs). Conventional compartmental PK models are often inadequate for capturing the site-specific kinetics of inhaled drugs.

Area covered

This review identifies the principal determinants of pulmonary drug absorption and critically examines how these elements can be incorporated into mechanistic pharmacokinetic (MPK) models. In addition, it highlights modeling strategies that simulate pulmonary drug kinetics, employing multiple approaches such as multiple-path particle dosimetry (MPPD), computational fluid dynamics (CFD), and physiologically based pharmacokinetic (PBPK) modeling to better represent particle deposition and the relevant lung physiology.

Expert opinion

MPK modeling represents a valuable strategy for progressing the development of inhaled therapies; however, critical barriers persist in aligning experimental measurements with physiologically meaningful predictions. Integration of detailed physiological parameters of the lung into MPK frameworks, in combination with state-of-the-art simulation techniques, will be mandatory for enhancing model reliability. Continuous model improvement will be essential for regulatory acceptance and for ensuring the successful translation of inhaled drugs into clinical practice.

By Ji Hoon Choi, Dong-Won Oh, Youn-Woong Choi, Jin-Hyuk Jeong, Ji-Hyeon Kwon, Chun-Woong Park & Yong-Bok Lee