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Enhanced Intranasal Absorption of Naltrexone by Dodecyl Maltopyranoside: Implications for the Treatment of Opioid Overdose

Based on its high affinity for μ opiate receptors and reported half‐life after oral administration, the pharmacokinetic properties of intranasal naltrexone were examined to evaluate its potential to treat opioid overdose. This study was prompted by the marked rise in overdose deaths linked to synthe...

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Autores principales: Krieter, Philip, Gyaw, Shwe, Chiang, C. Nora, Crystal, Roger, Skolnick, Phil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548568/
https://www.ncbi.nlm.nih.gov/pubmed/30698833
http://dx.doi.org/10.1002/jcph.1384
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author Krieter, Philip
Gyaw, Shwe
Chiang, C. Nora
Crystal, Roger
Skolnick, Phil
author_facet Krieter, Philip
Gyaw, Shwe
Chiang, C. Nora
Crystal, Roger
Skolnick, Phil
author_sort Krieter, Philip
collection PubMed
description Based on its high affinity for μ opiate receptors and reported half‐life after oral administration, the pharmacokinetic properties of intranasal naltrexone were examined to evaluate its potential to treat opioid overdose. This study was prompted by the marked rise in overdose deaths linked to synthetic opioids like fentanyl, which may require more potent, longer‐lived opiate antagonists than naloxone. Both the maximum plasma concentration (C(max)) and the time (T(max)) to reach C(max) for intranasal naltrexone (4 mg) were comparable to values reported for a Food and Drug Administration‐approved 4‐mg dose of intranasal naloxone. The addition of the absorption enhancer dodecyl maltoside (Intravail) increased C(max) by ∼3‐fold and reduced the T(max) from 0.5 to 0.17 hours. Despite these very rapid increases in plasma concentrations of naltrexone, its short half‐life following intranasal administration (∼2.2 hours) could limit its usefulness as a rescue medication, particularly against longer‐lived synthetic opioids. Nonetheless, the ability to rapidly attain high plasma concentrations of naltrexone may be useful in other indications, including an as‐needed dosing strategy to treat alcohol use disorder.
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spelling pubmed-65485682019-07-08 Enhanced Intranasal Absorption of Naltrexone by Dodecyl Maltopyranoside: Implications for the Treatment of Opioid Overdose Krieter, Philip Gyaw, Shwe Chiang, C. Nora Crystal, Roger Skolnick, Phil J Clin Pharmacol Pharmacokinetics Based on its high affinity for μ opiate receptors and reported half‐life after oral administration, the pharmacokinetic properties of intranasal naltrexone were examined to evaluate its potential to treat opioid overdose. This study was prompted by the marked rise in overdose deaths linked to synthetic opioids like fentanyl, which may require more potent, longer‐lived opiate antagonists than naloxone. Both the maximum plasma concentration (C(max)) and the time (T(max)) to reach C(max) for intranasal naltrexone (4 mg) were comparable to values reported for a Food and Drug Administration‐approved 4‐mg dose of intranasal naloxone. The addition of the absorption enhancer dodecyl maltoside (Intravail) increased C(max) by ∼3‐fold and reduced the T(max) from 0.5 to 0.17 hours. Despite these very rapid increases in plasma concentrations of naltrexone, its short half‐life following intranasal administration (∼2.2 hours) could limit its usefulness as a rescue medication, particularly against longer‐lived synthetic opioids. Nonetheless, the ability to rapidly attain high plasma concentrations of naltrexone may be useful in other indications, including an as‐needed dosing strategy to treat alcohol use disorder. John Wiley and Sons Inc. 2019-01-30 2019-07 /pmc/articles/PMC6548568/ /pubmed/30698833 http://dx.doi.org/10.1002/jcph.1384 Text en © 2019 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Pharmacokinetics
Krieter, Philip
Gyaw, Shwe
Chiang, C. Nora
Crystal, Roger
Skolnick, Phil
Enhanced Intranasal Absorption of Naltrexone by Dodecyl Maltopyranoside: Implications for the Treatment of Opioid Overdose
title Enhanced Intranasal Absorption of Naltrexone by Dodecyl Maltopyranoside: Implications for the Treatment of Opioid Overdose
title_full Enhanced Intranasal Absorption of Naltrexone by Dodecyl Maltopyranoside: Implications for the Treatment of Opioid Overdose
title_fullStr Enhanced Intranasal Absorption of Naltrexone by Dodecyl Maltopyranoside: Implications for the Treatment of Opioid Overdose
title_full_unstemmed Enhanced Intranasal Absorption of Naltrexone by Dodecyl Maltopyranoside: Implications for the Treatment of Opioid Overdose
title_short Enhanced Intranasal Absorption of Naltrexone by Dodecyl Maltopyranoside: Implications for the Treatment of Opioid Overdose
title_sort enhanced intranasal absorption of naltrexone by dodecyl maltopyranoside: implications for the treatment of opioid overdose
topic Pharmacokinetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548568/
https://www.ncbi.nlm.nih.gov/pubmed/30698833
http://dx.doi.org/10.1002/jcph.1384
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