TY - JOUR
T1 - Mice-to-men comparison of inhaled drug-aerosol deposition and clearance
AU - Kolanjiyil, Arun V.
AU - Kleinstreuer, Clement
AU - Kleinstreuer, Nicole C.
AU - Pham, Wellington
AU - Sadikot, Ruxana T.
N1 - Funding Information:
The authors gratefully acknowledge Dr. Rick Corley and colleagues at Pacific Northwest National Laboratory for providing the representative mouse nasopharyngeal geometry. The authors acknowledge the use of Fluent and ICEM software from Ansys, Inc. (Canonsburg, PA) as part of the NCSU-Ansys Professional Partnership. This work was partially funded by a grant from NIH , R01CA16700 .
Funding Information:
The authors gratefully acknowledge Dr. Rick Corley and colleagues at Pacific Northwest National Laboratory for providing the representative mouse nasopharyngeal geometry. The authors acknowledge the use of Fluent and ICEM software from Ansys, Inc. (Canonsburg, PA) as part of the NCSU-Ansys Professional Partnership. This work was partially funded by a grant from NIH, R01CA16700.
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
KW - Dose extrapolation
KW - Human lung model
KW - Lung deposition
KW - Mouse lung model
KW - Pharmacokinetics
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U2 - 10.1016/j.resp.2018.11.003
DO - 10.1016/j.resp.2018.11.003
M3 - Article
C2 - 30445230
AN - SCOPUS:85056694471
SN - 1569-9048
VL - 260
SP - 82
EP - 94
JO - Respiratory Physiology and Neurobiology
JF - Respiratory Physiology and Neurobiology
ER -