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1,1-Difluoroethane Detection Time in Blood after Inhalation Abuse Estimated by Monte Carlo PBPK Modeling

(1) Background: Inhalant abuse and misuse are still widespread problems. 1,1-Difluoroethane abuse is reported to be potentially fatal and to cause acute and chronic adverse health effects. Lab testing for difluoroethane is seldom done, partly because the maximum detection time (MDT) is unknown. We s...

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Autores principales: Huet, Raul, Johanson, Gunnar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588963/
https://www.ncbi.nlm.nih.gov/pubmed/33092229
http://dx.doi.org/10.3390/pharmaceutics12100997
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author Huet, Raul
Johanson, Gunnar
author_facet Huet, Raul
Johanson, Gunnar
author_sort Huet, Raul
collection PubMed
description (1) Background: Inhalant abuse and misuse are still widespread problems. 1,1-Difluoroethane abuse is reported to be potentially fatal and to cause acute and chronic adverse health effects. Lab testing for difluoroethane is seldom done, partly because the maximum detection time (MDT) is unknown. We sought to reliably estimate the MDT of difluoroethane in blood after inhalation abuse; (2) Methods: MDT were estimated for the adult male American population using a physiologically based pharmacokinetic (PBPK) model and abuse patterns detailed by two individuals. Based on sensitivity analyses, variability in huffing pattern and body mass index was introduced in the model by Monte Carlo simulation; (3) Results: With a detection limit of 0.14 mg/L, the median MDT was estimated to be 10.5 h (5th–95th percentile 7.8–12.8 h) after the 2-h abuse scenario and 13.5 h (10.5–15.8 h) after the 6-h scenario. The ranges reflect variability in body mass index and hence amount of body fat; (4) Conclusions: Our simulations suggest that the MDT of difluoroethane in blood after abuse ranges from 7.8 to 15.8 h. Although shorter compared to many other drugs, these MDT are sufficient to allow for testing several hours after suspected intoxication in a patient.
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spelling pubmed-75889632020-10-29 1,1-Difluoroethane Detection Time in Blood after Inhalation Abuse Estimated by Monte Carlo PBPK Modeling Huet, Raul Johanson, Gunnar Pharmaceutics Article (1) Background: Inhalant abuse and misuse are still widespread problems. 1,1-Difluoroethane abuse is reported to be potentially fatal and to cause acute and chronic adverse health effects. Lab testing for difluoroethane is seldom done, partly because the maximum detection time (MDT) is unknown. We sought to reliably estimate the MDT of difluoroethane in blood after inhalation abuse; (2) Methods: MDT were estimated for the adult male American population using a physiologically based pharmacokinetic (PBPK) model and abuse patterns detailed by two individuals. Based on sensitivity analyses, variability in huffing pattern and body mass index was introduced in the model by Monte Carlo simulation; (3) Results: With a detection limit of 0.14 mg/L, the median MDT was estimated to be 10.5 h (5th–95th percentile 7.8–12.8 h) after the 2-h abuse scenario and 13.5 h (10.5–15.8 h) after the 6-h scenario. The ranges reflect variability in body mass index and hence amount of body fat; (4) Conclusions: Our simulations suggest that the MDT of difluoroethane in blood after abuse ranges from 7.8 to 15.8 h. Although shorter compared to many other drugs, these MDT are sufficient to allow for testing several hours after suspected intoxication in a patient. MDPI 2020-10-20 /pmc/articles/PMC7588963/ /pubmed/33092229 http://dx.doi.org/10.3390/pharmaceutics12100997 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huet, Raul
Johanson, Gunnar
1,1-Difluoroethane Detection Time in Blood after Inhalation Abuse Estimated by Monte Carlo PBPK Modeling
title 1,1-Difluoroethane Detection Time in Blood after Inhalation Abuse Estimated by Monte Carlo PBPK Modeling
title_full 1,1-Difluoroethane Detection Time in Blood after Inhalation Abuse Estimated by Monte Carlo PBPK Modeling
title_fullStr 1,1-Difluoroethane Detection Time in Blood after Inhalation Abuse Estimated by Monte Carlo PBPK Modeling
title_full_unstemmed 1,1-Difluoroethane Detection Time in Blood after Inhalation Abuse Estimated by Monte Carlo PBPK Modeling
title_short 1,1-Difluoroethane Detection Time in Blood after Inhalation Abuse Estimated by Monte Carlo PBPK Modeling
title_sort 1,1-difluoroethane detection time in blood after inhalation abuse estimated by monte carlo pbpk modeling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588963/
https://www.ncbi.nlm.nih.gov/pubmed/33092229
http://dx.doi.org/10.3390/pharmaceutics12100997
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