{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T01:22:17Z","timestamp":1792372937185,"version":"4.4.0"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100011110","name":"UCB","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011110","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Staccato\u00ae alprazolam is a hand\u2010held inhalation device that provides rapid systemic delivery of alprazolam through the intrapulmonary route. This trial explored the pharmacokinetics and tolerability of single\u2010dose Staccato alprazolam 2\u2009mg in adolescents with epilepsy. Pharmacokinetic data were included in a population pharmacokinetic analysis to support adolescent dose selection in the Phase 3 trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Multicenter, Phase 1, open\u2010label trial in adolescents (12\u201317\u2009years) with focal, generalized, or focal and generalized epilepsy (UP0100\/NCT04857307). A single dose of Staccato alprazolam 2\u2009mg was administered in the morning following overnight fast. Pharmacokinetic data were used to update an existing population pharmacokinetic model in adults, which was used to investigate dosing in adolescents with epilepsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fourteen patients (6 weighing &lt;50\u2009kg, 8 weighing \u226550\u2009kg) were enrolled and administered Staccato alprazolam 2\u2009mg. Individual plasma alprazolam concentration\u2212time profiles indicated generally rapid absorption (median time to maximum plasma concentration [\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ]: 10.5 [range: 2\u2013120] min) with linear elimination. Geometric mean\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      , area under the plasma concentration\u2013time curve (AUC) from time 0 to last quantifiable concentration (AUC\n                      <jats:sub>0\u2013t<\/jats:sub>\n                      ), AUC from time 0 to infinity (AUC\n                      <jats:sub>inf<\/jats:sub>\n                      ), and apparent total body clearance (CL\/\n                      <jats:italic>F<\/jats:italic>\n                      ) were similar across body weight groups (&lt;50\u2009kg, \u226550\u2009kg). Three patients in the \u226550\u2009kg group reported treatment\u2010emergent adverse events (TEAEs), including dysgeusia, somnolence, dizziness, cough, and hiccups. No severe or serious TEAEs were reported. Simulations of exposure estimates using the updated population pharmacokinetic model indicated similar exposure (AUC\n                      <jats:sub>inf<\/jats:sub>\n                      ) for adolescents administered Staccato alprazolam 2\u2009mg compared with the adult reference range, with a slight increase in\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      at lower body weight.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Alprazolam was rapidly absorbed in most adolescent patients with epilepsy following administration with the Staccato device. No clinically relevant differences between body weight groups were observed on primary pharmacokinetic or safety outcomes. Staccato alprazolam 2\u2009mg was well tolerated. Overall, the present data support the use of Staccato alprazolam 2\u2009mg in adolescents with epilepsy (12\u201317\u2009years of age).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18643","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T09:44:53Z","timestamp":1761299093000},"page":"109-119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetics and tolerability of single\u2010dose Staccato\u00ae alprazolam in adolescents with epilepsy, and population pharmacokinetic analysis to support dose selection in adolescents"],"prefix":"10.1111","volume":"67","author":[{"given":"Pavel","family":"Klein","sequence":"first","affiliation":[{"name":"Department of Epilepsy Mid\u2010Atlantic Epilepsy and Sleep Center  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gewalin","family":"Aungaroon","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center, Division of Neurology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Biton","sequence":"additional","affiliation":[{"name":"Arkansas Epilepsy Program  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kore Kai","family":"Liow","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center Hawaii Pacific Neuroscience  Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Neurology Mary Bridge Children's Hospital, MultiCare Institute for Research and Innovation  Tacoma Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1710-4888","authenticated-orcid":false,"given":"Thomas","family":"Wychowski","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Sadek","sequence":"additional","affiliation":[{"name":"Research Institute of Orlando  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan\u2010Peer","family":"Elshoff","sequence":"additional","affiliation":[{"name":"Department of Global Clinical Development UCB  Monheim am Rhein Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Roebling","sequence":"additional","affiliation":[{"name":"Department of Global Clinical Development UCB  Monheim am Rhein Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliceson","family":"King","sequence":"additional","affiliation":[{"name":"Department of Safety Risk Management UCB  Smyrna Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara C.","family":"Rospo","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine UCB  Braine\u2010l'Alleud Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rik","family":"Schoemaker","sequence":"additional","affiliation":[{"name":"Occams Co\u00f6peratie U.A.  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