{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T22:37:04Z","timestamp":1772491024658,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Sex differences in drug pharmacokinetics include variations in the expression of the cytochrome P450 enzymes, which are involved in the metabolism of benzodiazepines. It is unclear whether sex influences outcomes associated with intranasally administered drugs. A post hoc analysis of sex differences was conducted to evaluate the effectiveness and safety of diazepam nasal spray, which included examining changes in the number of days between seizure clusters over time (SEIzure interVAL [SEIVAL]). Diazepam nasal spray is approved for acute treatment of seizure clusters in patients with epilepsy aged \u22656\u2009years. Data from a phase 3 safety study were used to determine the proportion of second doses used within 24\u2009h (ie, a proxy for effectiveness) and SEIVAL. Adverse events were recorded. Of 163 treated patients, 89 were female, and 74 were male. Approximately 16% of both sexes self\u2010administered the study drug. A slightly higher proportion of seizure clusters was treated with a second dose in female (14.7%) than male (9.4%) patients. SEIVAL increased significantly and substantially over a year for all patients. The safety profile was generally similar between the sexes. These results suggest that potential sex differences in benzodiazepine pharmacokinetics do not meaningfully influence outcomes associated with diazepam nasal spray.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>Some drugs may have differences in absorption and metabolism between genders that could translate into differences in safety and effectiveness. This safety study looked at diazepam nasal spray for treating seizure clusters in patients at least 6\u2009years old. It found that safety was about the same for females and males. For both groups, most clusters stopped after only 1 dose of the drug, and the time between treated clusters got longer over a year.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12907","type":"journal-article","created":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T06:44:55Z","timestamp":1707547495000},"page":"793-799","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Safety and effectiveness of diazepam nasal spray in male and female patients: Post hoc analysis of data from a phase 3 safety study"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4735-3431","authenticated-orcid":false,"given":"James W.","family":"Wheless","sequence":"first","affiliation":[{"name":"Le Bonheur Children's Hospital University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2272-5005","authenticated-orcid":false,"given":"Robert Edward","family":"Hogan","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis  St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles S.","family":"Davis","sequence":"additional","affiliation":[{"name":"CSD Biostatistics  Oro Valley Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8788-0722","authenticated-orcid":false,"given":"Enrique","family":"Carrazana","sequence":"additional","affiliation":[{"name":"Neurelis, Inc.  San Diego California USA"},{"name":"University of Hawaii John A. Burns School of Medicine  Honolulu Hawaii USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1299-0606","authenticated-orcid":false,"given":"Adrian L.","family":"Rabinowicz","sequence":"additional","affiliation":[{"name":"Neurelis, Inc.  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,2,10]]},"reference":[{"key":"e_1_2_14_2_1","first-page":"41","article-title":"Choosing antiepileptic drugs","author":"Doyle A","year":"2018","journal-title":"Pract Neurol"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-023-00511-0"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm13030489"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/can.2022.0345"},{"issue":"11","key":"e_1_2_14_6_1","first-page":"1254","article-title":"Sex\u2010based differences in drug activity","volume":"80","author":"Whitley H","year":"2009","journal-title":"Am Fam Physician"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11096-020-01212-z"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ehjcvp\/pvw042"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.44.101802.121453"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12362"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/187103"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2004.07.009"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.05.013"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/NRL.0000000000000140"},{"key":"e_1_2_14_15_1","volume-title":"VALTOCO\u00ae (diazepam nasal spray). 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