Mice-to-men comparison of inhaled drug-aerosol deposition and clearance

Arun V. Kolanjiyil, Clement Kleinstreuer, Nicole C. Kleinstreuer, Wellington Pham, Ruxana T. Sadikot

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Part of the effective prediction of the pharmacokinetics of drugs (or toxic particles) requires extrapolation of experimental data sets from animal studies to humans. As the respiratory tracts of rodents and humans are anatomically very different, there is a need to study airflow and drug-aerosol deposition patterns in lung airways of these laboratory animals and compare them to those of human lungs. As a first step, interspecies computational comparison modeling of inhaled nano-to-micron size drugs (50 nm < d< 15μm) was performed using mouse and human upper airway models under realistic breathing conditions. Critical species-specific differences in lung physiology of the upper airways and subsequently in local drug deposition were simulated and analyzed. In addition, a hybrid modeling methodology, combining Computational Fluid-Particle Dynamics (CF-PD) simulations with deterministic lung deposition models, was developed and predicted total and regional drug-aerosol depositions in lung airways of both mouse and man were compared, accounting for the geometric, kinematic and dynamic differences. Interestingly, our results indicate that the total particle deposition fractions, especially for submicron particles, are comparable in rodent and human respiratory models for corresponding breathing conditions. However, care must be taken when extrapolating a given dosage as considerable differences were noted in the regional particle deposition pattern. Combined with the deposition model, the particle retention and clearance kinetics of deposited nanoparticles indicates that the clearance rate from the mouse lung is higher than that in the human lung. In summary, the presented computer simulation models provide detailed fluid-particle dynamics results for upper lung airways of representative human and mouse models with a comparative analysis of particle lung deposition data, including a novel mice-to-men correlation as well as a particle-clearance analysis both useful for pharmacokinetic and toxicokinetic studies.

Original languageEnglish (US)
Pages (from-to)82-94
Number of pages13
JournalRespiratory Physiology and Neurobiology
Volume260
DOIs
StatePublished - Feb 2019
Externally publishedYes

Keywords

  • Dose extrapolation
  • Human lung model
  • Lung deposition
  • Mouse lung model
  • Pharmacokinetics

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pulmonary and Respiratory Medicine

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