{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T19:54:52Z","timestamp":1770839692283,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The pharmacokinetics of oral diazepam are affected by food, but food\u2010effect 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This randomized, open\u2010label crossover study compared equal doses of diazepam nasal spray after an overnight fast and after a standardized high\u2010fat, high\u2010calorie breakfast. Each participant served as their own control, and there was a washout period of at least 21\u2009days between treatments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010four healthy adults enrolled in this study. Two participants withdrew consent, and two had pre\u2010dose diazepam concentrations that exceeded the protocol\u2010defined 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% (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001) and the overall diazepam exposure during the first 4\u2009h was reduced by 57% (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001) compared with fasted conditions. The time to maximum plasma concentration was 4.0\u00a0h in the fed state compared with 2.0\u00a0h in the fasted state (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001). At 2\u2009h post\u2010dose, diazepam concentrations were \u2265150\u2009ng\/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\u00a0fed conditions (54.5%; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.0340).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17459","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T15:04:02Z","timestamp":1669129442000},"page":"364-373","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A randomized, open\u2010label, two\u2010treatment crossover study to evaluate the effect of food on the pharmacokinetics of diazepam nasal spray in healthy adults"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3296-8193","authenticated-orcid":false,"given":"Michael A.","family":"Rogawski","sequence":"first","affiliation":[{"name":"Departments of Neurology and Pharmacology, School of Medicine University of California, Davis  Sacramento California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2680-6304","authenticated-orcid":false,"given":"Gary","family":"Slatko","sequence":"additional","affiliation":[{"name":"Aquestive Therapeutics  Warren New\u00a0Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"Full prescribing information","author":"Valium\u00ae (diazepam) C\u2010IV","year":"2021"},{"key":"e_1_2_11_3_1","volume-title":"Full prescribing information","author":"Valtoco\u00ae (diazepam nasal spray) C\u2010IV","year":"2022"},{"key":"e_1_2_11_4_1","unstructured":"U.S. Food and Drug Administration.Drugs@FDA: FDA\u2010approved drugs. 2022. 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