{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:58:13Z","timestamp":1791374293134,"version":"4.3.1"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2024,3]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n To compare the safety and pharmacokinetics (PK) of dihydroergotamine (DHE) after administration of intranasal DHE powder (STS101), liquid nasal spray (LNS) DHE mesylate, and intramuscular (IM) DHE mesylate injection in healthy participants.<\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n DHE is an effective acute migraine treatment; however, self\u2010administration difficulties have prevented its broader role in the management of migraine.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This randomized, active\u2010controlled, five\u2010period crossover study was conducted over 5\u2009weeks separated by 1\u2010week washout periods. Three STS101 dosage strengths (5.2, 7.0, 8.6\u2009mg), and one dose each of LNS DHE 2.0\u2009mg, and IM DHE 1.0\u2009mg, were administered to 36 healthy participants. Liquid chromatography, tandem mass spectrometry was used to determine DHE (including its 8\u2032OH\u2010DHE metabolite) plasma levels and to calculate PK parameters (\n C<\/jats:italic>\n max<\/jats:sub>\n ,\n T<\/jats:italic>\n max<\/jats:sub>\n , AUC\n 0\u20102h<\/jats:sub>\n , AUC\n 0\u2010last<\/jats:sub>\n , AUC\n 0\u2010inf<\/jats:sub>\n , and\n t<\/jats:italic>\n 1\/2<\/jats:sub>\n ). Safety was evaluated by monitoring adverse events (AEs), vital signs, electrocardiograms, nasal examinations, and laboratory parameters.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Thirty\u2010six participants (mean age 36\u2009years; 19% Hispanic Black and 81% Hispanic White) were enrolled. DHE plasma concentrations rose rapidly after STS101 5.2, 7.0, and 8.6\u2009mg and IM DHE injection, with mean concentrations greater than 2000\u2009pg\/mL for all STS101 dose strengths at 20\u2009min. All STS101 dose strengths showed approximately 3\u2010fold higher\n C<\/jats:italic>\n max<\/jats:sub>\n , AUC\n 0\u20102h<\/jats:sub>\n , and AUC\n 0\u2010inf<\/jats:sub>\n , than the LNS DHE. The mean AUC\n 0\u2010inf<\/jats:sub>\n of STS101 7.0 and 8.6\u2009mg were comparable to IM DHE (12,600 and 13,200 vs. 13,400\u2009h \u00d7 pg\/mL). All STS101 dose strengths showed substantially lower variability (CV%) compared to LNS DHE for\n C<\/jats:italic>\n max<\/jats:sub>\n (35%\u201341% vs. 87%), and AUC\n 0\u2010inf<\/jats:sub>\n (37%\u201346% vs. 65%). STS101 was well tolerated, and all treatment\u2010emergent AEs were mild and transient.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n STS101 showed rapid absorption and was well tolerated with mild and transient treatment\u2010emergent AEs. Achieving effective DHE plasma concentrations within 10\u2009min, STS101 displayed a favorable PK profile relative to the LNS with higher\n C<\/jats:italic>\n max<\/jats:sub>\n , AUC\n 0\u20102h<\/jats:sub>\n , and AUC\n 0inf<\/jats:sub>\n , and with greater response consistency. The AUC\n 0\u2010inf<\/jats:sub>\n was comparable to IM DHE.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/head.14685","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T23:08:34Z","timestamp":1709075314000},"page":"266-275","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A randomized, open\u2010label, 5\u2010period crossover study evaluating the pharmacokinetics and safety of a single dose of intranasal dihydroergotamine (DHE) powder (STS101), intramuscular DHE mesylate, and liquid nasal spray DHE in healthy adults"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2652-2897","authenticated-orcid":false,"given":"Richard B.","family":"Lipton","sequence":"first","affiliation":[{"name":"Department of Neurology Montefiore Headache Center Albert Einstein College of Medicine Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlef","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Satsuma Pharmaceuticals Inc. Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bermudez","sequence":"additional","affiliation":[{"name":"Quotient Sciences Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry","family":"Hu","sequence":"additional","affiliation":[{"name":"Allucent Gary North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Hussey","sequence":"additional","affiliation":[{"name":"Allucent Gary North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Levy","sequence":"additional","affiliation":[{"name":"Quotient Sciences Miami Florida 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