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The nose is an attractive alternative route of drug delivery since it provides patient convenience of at-home use, gastrointestinal (GI) avoidance, and rapid absorption of drugs into systemic circulation because of its large surface area. However, the site of drug deposition within the nasal cavity should be considered since it can influence drug absorption. Traditional nasal devices have been shown to target drug delivery to the lower nasal space where epithelium is not best-suited for drug absorption and where there is an increased likelihood of drug clearance due to nasal drip, swallowing, or mucociliary clearance, potentially resulting in variable absorption and suboptimal efficacy. Alternatively, the upper nasal space (UNS) offers a permeable, richly vascularized epithelium with a decreased likelihood of drug loss or clearance due to the anatomy of this area. Traditional nasal pumps deposit &lt;5% of active drug into the UNS because of the nasal cavity's complex architecture. A new technology, Precision Olfactory Delivery (POD\n                    <jats:sup>\u00ae<\/jats:sup>\n                    ), is a handheld, manually actuated, propellant-powered, administration device that delivers drug specifically to the UNS. A dihydroergotamine (DHE) mesylate product, INP104, utilizes POD technology to deliver drug to the UNS for the acute treatment of migraine. Results from clinical studies of INP104 demonstrate a favorable pharmacokinetic profile, consistent and predictable dosing, rapid systemic levels known to be effective (similar to other DHE mesylate clinical programs), safety and tolerability on the upper nasal mucosa, and high patient acceptance. POD technology may have the potential to overcome the limitations of traditional nasal delivery systems, while utilizing the nasal delivery benefits of GI tract avoidance, rapid onset, patient convenience, and ease of use.\n                  <\/jats:p>","DOI":"10.1089\/jamp.2022.0005","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T17:01:35Z","timestamp":1663261295000},"page":"321-332","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":21,"title":["Delivery of Dihydroergotamine Mesylate to the Upper Nasal Space for the Acute Treatment of Migraine: Technology in Action"],"prefix":"10.1177","volume":"35","author":[{"given":"Wade","family":"Cooper","sequence":"first","affiliation":[{"name":"Headache and Neuropathic Pain Program, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sutapa","family":"Ray","sequence":"additional","affiliation":[{"name":"Impel Pharmaceuticals, Seattle, Washington, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheena K.","family":"Aurora","sequence":"additional","affiliation":[{"name":"Impel Pharmaceuticals, Seattle, Washington, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9892-3695","authenticated-orcid":false,"given":"Stephen B.","family":"Shrewsbury","sequence":"additional","affiliation":[{"name":"Impel Pharmaceuticals, Seattle, Washington, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Fuller","sequence":"additional","affiliation":[{"name":"Impel Pharmaceuticals, Seattle, Washington, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg","family":"Davies","sequence":"additional","affiliation":[{"name":"Impel Pharmaceuticals, Seattle, Washington, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Hoekman","sequence":"additional","affiliation":[{"name":"Impel Pharmaceuticals, Seattle, Washington, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.12186"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201606596"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics11030129"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b14-00398"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.07.006"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(97)00059-8"},{"key":"e_1_3_6_8_2","unstructured":"Allergan receives FDA complete response letter for migraine drug Semprana. 2014. https:\/\/www.dcatvci.org\/pharmanews\/%201837-allergan-receives-fda-complete-responseletter-for-migraine-drug-semprana Accessed August18 2020."},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2006.00311.x"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.13700"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13346-012-0108-9"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2005.07.009"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics10030116"},{"key":"e_1_3_6_14_2","volume-title":"Neuroanatomy, Cranial Nerve 1 (Olfactory)","author":"Helwany M","unstructured":"Helwany M, , and Bordoni B: Neuroanatomy, Cranial Nerve 1 (Olfactory). 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