{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:49:25Z","timestamp":1787014165088,"version":"build-2736575974"},"reference-count":19,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,8,25]],"date-time":"2014-08-25T00:00:00Z","timestamp":1408924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To determine the feasibility of administering a diazepam nasal spray formulation (diazepam\u2010\n                      <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>\n                      ) to adults with epilepsy during a generalized tonic\u2013clonic seizure or in the postictal period following a tonic\u2013clonic or other seizure type, to assess pharmacokinetics and to assess tolerability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An open\u2010label study was conducted in patients admitted to the epilepsy monitoring unit. Eligible patients received a single dose of diazepam\u2010\n                      <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>\n                      approximating 0.2\u00a0mg\/kg. Plasma diazepam concentrations were measured serially up to 12\u00a0h postdose, and maximum observed plasma concentration (C\n                      <jats:sub>max<\/jats:sub>\n                      ); time to maximum concentration (T\n                      <jats:sub>max<\/jats:sub>\n                      ); and the area under the plasma concentration\u2013time curve for time zero to last sampling time (AUC\n                      <jats:sub>0\u201312<\/jats:sub>\n                      ) were estimated and dose\u2010normalized. Pharmacodynamic assessments included Kaplan\u2010Meier analysis to determine the time\u2010to\u2010next seizure. Safety and tolerability were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 78 patients who consented, 30 had treatment and pharmacokinetic data. Ten patients were treated during a convulsive tonic\u2013clonic seizure, seven within 5\u00a0min following the last clonic jerk, and 13 in the postictal period \u22655\u00a0min after a tonic\u2013clonic or following other seizure\u2010types. Diazepam median T\n                      <jats:sub>max<\/jats:sub>\n                      was 45\u00a0min. Dose\u2010normalized mean C\n                      <jats:sub>max<\/jats:sub>\n                      and\n                      <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>\n                      <jats:sub>0\u201312<\/jats:sub>\n                      values of diazepam were comparable among patients regardless of the timing of diazepam\u2010\n                      <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>\n                      administration in relation to seizure. Of those treated, 65% were seizure\u2010free during the 12\u2010h observation period and 35% had post\u2010dose seizures. Treatment was well tolerated, with no unexpected safety findings: 74% had mild and 25% had moderate adverse events. Nasopharyngeal signs were resolved by 12\u00a0h postdose.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Diazepam can be delivered in effective therapeutic concentrations by a nasal spray device during the convulsive phase of tonic\u2013clonic seizures or in the postictal periods following tonic\u2013clonic or other seizure types.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.12755","type":"journal-article","created":{"date-parts":[[2014,8,25]],"date-time":"2014-08-25T14:06:04Z","timestamp":1408975564000},"page":"1544-1550","source":"Crossref","is-referenced-by-count":26,"title":["Dosing feasibility and tolerability of intranasal diazepam in adults with epilepsy"],"prefix":"10.1111","volume":"55","author":[{"given":"Michael R.","family":"Sperling","sequence":"first","affiliation":[{"name":"Thomas Jefferson University Philadelphia Pennsylvania U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin F.","family":"Haas","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center Nashville Tennessee U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Krauss","sequence":"additional","affiliation":[{"name":"Johns Hopkins University Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussam","family":"Seif Eddeine","sequence":"additional","affiliation":[{"name":"St. Joseph's Hospital and Medical Center Phoenix Arizona U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Herbert R.","family":"Henney","sequence":"additional","affiliation":[{"name":"Acorda Therapeutics, Inc. Ardsley New York U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian L.","family":"Rabinowicz","sequence":"additional","affiliation":[{"name":"Acorda Therapeutics, Inc. Ardsley New York U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Bream","sequence":"additional","affiliation":[{"name":"Aerial Biopharma LLC Morrisville North Carolina U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Squillacote","sequence":"additional","affiliation":[{"name":"Acorda Therapeutics, Inc. Ardsley New York U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique J.","family":"Carrazana","sequence":"additional","affiliation":[{"name":"Acorda Therapeutics, Inc. 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