A Partial Differential Equation Approach to Inhalation Physiologically Based Pharmacokinetic Modeling
Journal article, 2018

CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics. The heterogeneous nature of the lungs and the range of processes affecting pulmonary drug disposition make prediction of inhaled drugs challenging. These predictions are critical, as the local exposure cannot be measured and current inhalation physiologically based pharmacokinetic (PBPK) models do not capture all necessary features. Utilizing partial differential equations, we present an inhalation PBPK model to describe the heterogeneity in both lung physiology and particle size. The model mechanistically describes important processes, such as deposition, mucociliary clearance, and dissolution. In addition, simplifications are introduced to reduce computational cost without loss of accuracy. Three case studies exemplify how the model can enhance our understanding of pulmonary drug disposition. Specific findings include that most small airways can be targeted by inhalation, and overdosing may eradicate the advantage of inhalation. The presented model can guide the design of inhaled molecules, formulations, as well as clinical trials, providing opportunities to explore regional targeting.

Author

Elin Boger

AstraZeneca AB

Oskar Wigström

Chalmers, Electrical Engineering, Systems and control

CPT: Pharmacometrics and Systems Pharmacology

21638306 (eISSN)

Vol. 7 10 638-646

Subject Categories

Pharmaceutical Sciences

Bioinformatics (Computational Biology)

Embedded Systems

DOI

10.1002/psp4.12344

PubMed

30084547

More information

Latest update

10/23/2022