title: Pharmacokinetic analysis of the chronic administration of the inert gases Xe and Ar using a physiological based model.
abstract: BACKGROUND
  New gas therapies using inert gases such as xenon and argon are being studied, which would require chronically administered repeating doses. The pharmacokinetics of this type of administration has not been addressed in the literature.
  
  
  METHODS
  A physiologically based pharmacokinetics (PBPK) model for humans, pigs, mice, and rats has been developed to investigate the unique aspects of the chronic administration of inert gas therapies. The absorption, distribution, metabolism and excretion (ADME) models are as follows: absorption in all compartments is assumed to be perfusion limited, no metabolism of the gases occurs, and excretion is only the reverse process of absorption through the lungs and exhaled.
  
  
  RESULTS
  The model has shown that there can be a residual dose, equivalent to constant administration, for chronic repeated dosing of xenon in humans. However, this is not necessarily the case for small animals used in pre-clinical studies.
  
  
  CONCLUSIONS
  The use of standard pharmacokinetics parameters such as area under the curve would be more appropriate to assess the delivered dose of chronic gas administration than the gas concentration in the delivery system that is typically reported in the scientific literature because species and gas differences can result in very different delivered doses.
authors.affiliation: Medical R&D, Air Liquide Santé International, Centre de Recherche Paris-Saclay, 1, chemin de la Porte des Loges, BP126 - 78354 Jouy en Josas, France ; Department of Mechanical Engineering, Lafayette College, Easton, PA 18042 USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Katz
authors.affiliation: Medical R&D, Air Liquide Santé International, Centre de Recherche Paris-Saclay, 1, chemin de la Porte des Loges, BP126 - 78354 Jouy en Josas, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Murdock
authors.affiliation: Medical R&D, Air Liquide Santé International, Centre de Recherche Paris-Saclay, 1, chemin de la Porte des Loges, BP126 - 78354 Jouy en Josas, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Palgen
authors.affiliation: Medical R&D, Air Liquide Santé International, Centre de Recherche Paris-Saclay, 1, chemin de la Porte des Loges, BP126 - 78354 Jouy en Josas, France.
authors.forename: Jan
authors.initials: J
authors.lastname: Pype
authors.affiliation: Medical R&D, Air Liquide Santé International, Centre de Recherche Paris-Saclay, 1, chemin de la Porte des Loges, BP126 - 78354 Jouy en Josas, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Caillibotte
keywords: Argon; Human; Pharmacokinetics; Pig; Rat; Xenon