{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:21:13Z","timestamp":1790803273374,"version":"4.1.0"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T00:00:00Z","timestamp":1707091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Etripamil, a fast\u2010acting nondihydropyridine L\u2010type calcium channel blocker, is under investigation for potential self\u2010administration for the acute treatment of supraventricular tachyarrhythmias in a medically unsupervised setting. We report detailed pharmacokinetics and pharmacodynamics of intranasally administered etripamil in healthy adults from 2 Phase 1, randomized, double\u2010blind studies: Study MSP\u20102017\u20101096 (sequential dose\u2010escalation, crossover study design, n = 64) and NODE\u2010102 (single dose, 4\u2010way crossover study, n = 24). Validated bioanalytical assays determined plasma concentrations of etripamil and its inactive metabolite. Noncompartmental pharmacokinetic parameters were calculated. Pharmacodynamic parameters were determined for PR interval, blood pressure, and heart rate. Etripamil was rapidly absorbed intranasally, with time to maximal plasma concentration of 5\u20108.5 minutes, corresponding to a rapid greater than 10% increase in mean maximum PR interval from baseline within 4\u20107 minutes of doses of 60\u00a0mg or greater. Following peak plasma concentrations, systemic etripamil levels declined rapidly within the first 15 minutes following dosing and decreased more gradually thereafter. PR interval prolongation greater than 10% from baseline was generally sustained for about 45 minutes at doses of 60\u00a0mg or greater. The mean terminal half\u2010life ranged from about 1.5 hours with 60\u00a0mg to about 2.5\u20103 hours for the 70\u2010 and 105\u2010mg doses. Etripamil was generally well tolerated without symptomatic hypotension. Adverse events were primarily mild to moderate and related to the administration site; no serious adverse events or episodes of atrioventricular block occurred. Intranasal etripamil administration, at doses of 60\u00a0mg or greater, produced rapidly occurring slowing of atrioventricular nodal conduction with a limited duration of effect without hemodynamic or electrocardiographic safety signals in healthy volunteers.<\/jats:p>","DOI":"10.1002\/cpdd.1383","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T07:13:58Z","timestamp":1707290038000},"page":"367-379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Pharmacokinetics and Pharmacodynamics of Etripamil, an Intranasally Administered, Fast\u2010Acting, Nondihydropyridine Calcium Channel Blocker"],"prefix":"10.1002","volume":"13","author":[{"given":"James E.","family":"Ip","sequence":"first","affiliation":[{"name":"Weill Cornell Medicine New York Presbyterian Hospital New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Wight","sequence":"additional","affiliation":[{"name":"Milestone Pharmaceuticals  Saint\u2010Laurent Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne Seng","family":"Yue","sequence":"additional","affiliation":[{"name":"Learn and Confirm Inc.  Saint\u2010Laurent Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Altasciences  Cypress CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Plat","sequence":"additional","affiliation":[{"name":"Milestone Pharmaceuticals  Saint\u2010Laurent Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce S.","family":"Stambler","sequence":"additional","affiliation":[{"name":"Piedmont Heart Institute  Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.108.789081"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000059743.36226.E8"},{"issue":"14","key":"e_1_2_9_4_1","first-page":"e471","article-title":"2015 ACC\/AHA\/HRS Guideline for the management of adult patients with supraventricular tachycardia: executive summary: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society","volume":"133","author":"Page RL","year":"2016","journal-title":"Circulation"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000041"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/20503121211017756"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40256-023-00592-7"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40256-023-00589-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00776-6"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.122.010915"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.04.082"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(03)00987-2"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1982.227"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz467"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jelectrocard.2011.06.003"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(97)00126-7"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht176"},{"key":"e_1_2_9_18_1","first-page":"S214","article-title":"S\u2010PO02\u2010194 Electrophysiological mechanism of action of inhaled etripamil on AV nodal refractoriness and conduction in subjects with paroxysmal supraventricular tachycardia (PSVT) in the NODE\u20101 trial","volume":"16","author":"Stambler BS","year":"2019","journal-title":"Heart Rhythm"},{"issue":"10","key":"e_1_2_9_19_1","first-page":"479","article-title":"High\u2010density mapping of the slow pathway in a patient with atrioventricular nodal reentry given intranasal Etripamil during the NODE\u20101 study","volume":"3","author":"Choe WC","year":"2017","journal-title":"Heart Rhythm Case Rep"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1383","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T06:15:34Z","timestamp":1716358534000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1383"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,5]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/cpdd.1383"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1383","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,5]]},"assertion":[{"value":"2023-08-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}