Gas transport duringin vitroandin vivopreclinical testing of inert gas therapies.
New gas therapies using inert gases such as xenon and argon are being studied, which requirein vitroandin vivopreclinical experiments. Examples of the kinetics of gas transport during such experiments are analyzed in this paper. Using analytical and numerical models, we analyze anin vitroexperiment for gas transport to a 96 cell well plate and anin vivodelivery to a small animal chamber, where the key processes considered are the wash-in of test gas into an apparatus dead volume, the diffusion of test gas through the liquid media in a well of a cell test plate, and the pharmacokinetics in a rat. In the case of small animals in a chamber, the key variable controlling the kinetics is the chamber wash-in time constant that is a function of the chamber volume and the gas flow rate. For cells covered by a liquid media the diffusion of gas through the liquid media is the dominant mechanism, such that liquid depth and the gas diffusion constant are the key parameters. The key message from these analyses is that the transport of gas during preclinical experiments can be important in determining the true dose as experienced at the site of action in an animal or to a cell.
Medical R&D, Air Liquide Santé International, Centre de Recherche Paris-Saclay, 78354, Jouy-en-Josas, France; Department of Mechanical Engineering, Lafayette College, Easton, PA, USA.
Ira
0000-0001-6755-9739
I
Katz
Medical R&D, Air Liquide Santé International, Centre de Recherche Paris-Saclay, 78354, Jouy-en-Josas, France.
Marc
M
Palgen
Medical R&D, Air Liquide Santé International, Centre de Recherche Paris-Saclay, 78354, Jouy-en-Josas, France.
Jacqueline
J
Murdock
Department of Mechanical Engineering, University of Alberta, Edmonton AB T6G 2G8, Canada.
Andrew R
AR
Martin
Medical R&D, Air Liquide Santé International, Centre de Recherche Paris-Saclay, 78354, Jouy-en-Josas, France.
Géraldine
G
Farjot
Medical R&D, Air Liquide Santé International, Centre de Recherche Paris-Saclay, 78354, Jouy-en-Josas, France.
Georges
G
Caillibotte
argon; neuroprotection; noble gases; organoprotection; pharmacokinetics; rats; xenon