Argon pharmacokinetics: measurements in pigs and analysis in humans using a physiologically based pharmacokinetics model.


Journal

Medical gas research
ISSN: 2045-9912
Titre abrégé: Med Gas Res
Pays: Australia
ID NLM: 101564536

Informations de publication

Date de publication:
01 Dec 2024
Historique:
received: 30 03 2023
accepted: 22 01 2024
medline: 29 7 2024
pubmed: 29 7 2024
entrez: 29 7 2024
Statut: ppublish

Résumé

The primary objective of this study was to investigate the pharmacokinetics of inhaled argon in young pigs using mechanical ventilation. Also a physiologically based model of argon pharmacokinetics (PBPK) is validated with human data for xenon from the literature and the new data from juvenile pigs. The inherent difficulty in performing pharmacokinetics studies of argon makes the use of the PBPK model especially relevant. The model is used to investigate argon pharmacokinetics for adult and neonate applications. Juvenile pigs (n = 4) were anesthetized, submitted to endotracheal intubation, and mechanical ventilation using a conventional ventilator. Argon inhalation was achieved by switching the animal from the first mechanical ventilator (with air/oxygen) to a second one that was supplied with 75% argon and 25% oxygen from premixed gas cylinders. This administration yielded blood samples that were analyzed using a quadrupole based technique for determining argon concentration. The range of blood:gas partition coefficient corresponding to the average measured Cmax of 190-872 μM is 0.005-0.022. Based on the average curve, T1/2= 75 seconds. The PBPK is shown to be in general agreement with the experimental data in pigs. Inhaled argon administration exhibited an on-off nature such that AUC was proportional to administration time. Confidence in the PBPK model and the remarkably robust and stable on-off nature of argon pharmacokinetics, notwithstanding intersubject variability and comorbidity, suggests that inhaled argon could readily be applied to any treatment regime.

Identifiants

pubmed: 39073329
doi: 10.4103/mgr.mgr_20_23
pii: 01612956-202414040-00011
doi:

Substances chimiques

Argon 67XQY1V3KH

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

206-212

Informations de copyright

Copyright © 2024 Copyright: © 2024 Medical Gas Research.

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Auteurs

Ira Katz (I)

Early Drug Development, Air Liquide Santé International, Les loges-en-Josas, France.

Renaud Tissier (R)

Univ Paris Est Créteil, Institut National de la Santé et de la Recherche Médicale, Mondor Institute for Biomedical Research, Créteil, France.
Ecole Nationale Vétérinaire d'Alfort, Mondor Institute for Biomedical Research, Maisons-Alfort, France.

Matthias Kohlhauer (M)

Univ Paris Est Créteil, Institut National de la Santé et de la Recherche Médicale, Mondor Institute for Biomedical Research, Créteil, France.
Ecole Nationale Vétérinaire d'Alfort, Mondor Institute for Biomedical Research, Maisons-Alfort, France.

Joël Lemaire (J)

Institut de Chimie Physique, Centre National de la Recherche Scientifique, Université Paris-Saclay, Orsay, France.

Arthur Hamlin (A)

Institut de Chimie Physique, Centre National de la Recherche Scientifique, Université Paris-Saclay, Orsay, France.

Matthieu Chalopin (M)

Early Drug Development, Air Liquide Santé International, Les loges-en-Josas, France.

Géraldine Farjot (G)

Early Drug Development, Air Liquide Santé International, Les loges-en-Josas, France.

Aude Milet (A)

Early Drug Development, Air Liquide Santé International, Les loges-en-Josas, France.

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Classifications MeSH