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A randomized, open‐label, two‐treatment crossover study to evaluate the effect of food on the pharmacokinetics of diazepam nasal spray in healthy adults
OBJECTIVE: The pharmacokinetics of oral diazepam are affected by food, but food‐effect studies have not been conducted for diazepam nasal spray because it is believed that most absorption occurs via the nasal mucosa. However, gastrointestinal side effects reported with nasal diazepam suggest that at...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10107174/ https://www.ncbi.nlm.nih.gov/pubmed/36413125 http://dx.doi.org/10.1111/epi.17459 |
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author | Rogawski, Michael A. Slatko, Gary |
author_facet | Rogawski, Michael A. Slatko, Gary |
author_sort | Rogawski, Michael A. |
collection | PubMed |
description | OBJECTIVE: The pharmacokinetics of oral diazepam are affected by food, but food‐effect studies have not been conducted for diazepam nasal spray because it is believed that most absorption occurs via the nasal mucosa. However, gastrointestinal side effects reported with nasal diazepam suggest that at least a portion of the drug may be absorbed enterally and thus subject to food effects. The objective of this study was to evaluate the possible effects of food on the pharmacokinetics of diazepam nasal spray in healthy adults. METHODS: This randomized, open‐label crossover study compared equal doses of diazepam nasal spray after an overnight fast and after a standardized high‐fat, high‐calorie breakfast. Each participant served as their own control, and there was a washout period of at least 21 days between treatments. RESULTS: Twenty‐four healthy adults enrolled in this study. Two participants withdrew consent, and two had pre‐dose diazepam concentrations that exceeded the protocol‐defined minimum after the washout period and were excluded from the final analysis population of 20 participants. Under fed conditions, the mean maximum plasma diazepam concentration was decreased by 48% (p < .0001) and the overall diazepam exposure during the first 4 h was reduced by 57% (p < .0001) compared with fasted conditions. The time to maximum plasma concentration was 4.0 h in the fed state compared with 2.0 h in the fasted state (p < .0001). At 2 h post‐dose, diazepam concentrations were ≥150 ng/mL for 100% of the participants when in the fasted state and 30% when in the fed state. Significantly more participants experienced adverse events under fasted conditions (83.3%) than under fed conditions (54.5%; p = .0340). SIGNIFICANCE: This study in healthy volunteers demonstrated that food significantly decreases and delays the absorption of diazepam dosed via nasal spray. Patients using diazepam nasal spray after eating may obtain diazepam concentrations that are below those needed for seizure control. |
format | Online Article Text |
id | pubmed-10107174 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101071742023-04-18 A randomized, open‐label, two‐treatment crossover study to evaluate the effect of food on the pharmacokinetics of diazepam nasal spray in healthy adults Rogawski, Michael A. Slatko, Gary Epilepsia Research Articles OBJECTIVE: The pharmacokinetics of oral diazepam are affected by food, but food‐effect studies have not been conducted for diazepam nasal spray because it is believed that most absorption occurs via the nasal mucosa. However, gastrointestinal side effects reported with nasal diazepam suggest that at least a portion of the drug may be absorbed enterally and thus subject to food effects. The objective of this study was to evaluate the possible effects of food on the pharmacokinetics of diazepam nasal spray in healthy adults. METHODS: This randomized, open‐label crossover study compared equal doses of diazepam nasal spray after an overnight fast and after a standardized high‐fat, high‐calorie breakfast. Each participant served as their own control, and there was a washout period of at least 21 days between treatments. RESULTS: Twenty‐four healthy adults enrolled in this study. Two participants withdrew consent, and two had pre‐dose diazepam concentrations that exceeded the protocol‐defined minimum after the washout period and were excluded from the final analysis population of 20 participants. Under fed conditions, the mean maximum plasma diazepam concentration was decreased by 48% (p < .0001) and the overall diazepam exposure during the first 4 h was reduced by 57% (p < .0001) compared with fasted conditions. The time to maximum plasma concentration was 4.0 h in the fed state compared with 2.0 h in the fasted state (p < .0001). At 2 h post‐dose, diazepam concentrations were ≥150 ng/mL for 100% of the participants when in the fasted state and 30% when in the fed state. Significantly more participants experienced adverse events under fasted conditions (83.3%) than under fed conditions (54.5%; p = .0340). SIGNIFICANCE: This study in healthy volunteers demonstrated that food significantly decreases and delays the absorption of diazepam dosed via nasal spray. Patients using diazepam nasal spray after eating may obtain diazepam concentrations that are below those needed for seizure control. John Wiley and Sons Inc. 2022-12-21 2023-02 /pmc/articles/PMC10107174/ /pubmed/36413125 http://dx.doi.org/10.1111/epi.17459 Text en © 2022 Aquestive Therapeutics. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://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 | Research Articles Rogawski, Michael A. Slatko, Gary A randomized, open‐label, two‐treatment crossover study to evaluate the effect of food on the pharmacokinetics of diazepam nasal spray in healthy adults |
title | A randomized, open‐label, two‐treatment crossover study to evaluate the effect of food on the pharmacokinetics of diazepam nasal spray in healthy adults |
title_full | A randomized, open‐label, two‐treatment crossover study to evaluate the effect of food on the pharmacokinetics of diazepam nasal spray in healthy adults |
title_fullStr | A randomized, open‐label, two‐treatment crossover study to evaluate the effect of food on the pharmacokinetics of diazepam nasal spray in healthy adults |
title_full_unstemmed | A randomized, open‐label, two‐treatment crossover study to evaluate the effect of food on the pharmacokinetics of diazepam nasal spray in healthy adults |
title_short | A randomized, open‐label, two‐treatment crossover study to evaluate the effect of food on the pharmacokinetics of diazepam nasal spray in healthy adults |
title_sort | randomized, open‐label, two‐treatment crossover study to evaluate the effect of food on the pharmacokinetics of diazepam nasal spray in healthy adults |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10107174/ https://www.ncbi.nlm.nih.gov/pubmed/36413125 http://dx.doi.org/10.1111/epi.17459 |
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