{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T15:31:45Z","timestamp":1777908705310,"version":"3.51.4"},"reference-count":27,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Aerosol Medicine and Pulmonary Drug Delivery"],"published-print":{"date-parts":[[2025,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Primatene\n                      <jats:sup>\u00ae<\/jats:sup>\n                      MIST, an epinephrine metered-dose inhaler (MDI), has long been questioned by some medical professionals for asthma treatment despite having been approved by the Food and Drug Administration. One of the primary reasons for their concerns stemmed from potential cardiovascular complications following epinephrine administration. However, the majority of documented cardiovascular complications seemed to occur following the injection route of the epinephrine. The aim of this study was to evaluate the systemic exposure of epinephrine delivered through different administration routes and to understand its relationship with cardiovascular effects. Since albuterol inhalers are commonly recommended for asthma, albuterol was also studied as a comparator drug.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method:<\/jats:title>\n                    <jats:p>A randomized, evaluator-blinded, three-arm crossover study was conducted in 28 healthy adult subjects to compare the profiles of systemic exposure for epinephrine delivered by MDI versus epinephrine intramuscular (IM) injection and albuterol MDI. Serially sampled plasma epinephrine and albuterol levels were measured and compared between treatment groups. Safety was assessed by adverse events, serial vital signs, electrocardiograms (ECGs), and clinical laboratory tests obtained at each crossover dosing visit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Systemic exogenous drug exposure for inhaled epinephrine MDI (39 pg\/mL \u00d7 hour) was \u223c9 times lower than that of epinephrine IM (435 pg\/mL \u00d7 hour) and 122 times lower than that of albuterol MDI (3453 pg\/mL \u00d7 hour) after dose normalization. The C\n                      <jats:sub>max<\/jats:sub>\n                      in epinephrine MDI (345 pg\/mL) was approximately half of that of epinephrine IM (816 pg\/mL) and that of albuterol MDI (681 pg\/mL). Plasma drug concentrations for epinephrine MDI dropped rapidly to baseline (\u223c0.6 hour), while epinephrine IM took \u223c8 hours, and albuterol MDI required more than 24 hours. Epinephrine MDI and albuterol MDI resulted in minimal, clinically insignificant changes in vital signs and ECGs, whereas epinephrine IM led to mild transient increases in systolic blood pressure, heart rate, and corrected QT interval.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Epinephrine MDI (Primatene MIST) had \u223c9 times lower systemic drug exposure (SDE) than that of epinephrine IM and \u223c122 times lower than that of albuterol MDI. The lower SDE of inhaled epinephrine also correlated with reassuring safety findings, with no significant cardiovascular adverse effects found, compared with transient effects seen after IM epinephrine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration number:<\/jats:title>\n                    <jats:p>NCT04207840.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jamp.2024.0025","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T10:04:11Z","timestamp":1724925851000},"page":"71-82","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparison of Systemic Exposure Between Epinephrine Delivered via Metered-Dose Inhalation and Intramuscular Injection"],"prefix":"10.1177","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2524-5074","authenticated-orcid":false,"given":"Jack Yongfeng","family":"Zhang","sequence":"first","affiliation":[{"name":"Amphastar Pharmaceuticals, Inc., Rancho Cucamonga, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Ziping","family":"Luo","sequence":"additional","affiliation":[{"name":"Amphastar Pharmaceuticals, Inc., Rancho Cucamonga, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tony","family":"Marrs","sequence":"additional","affiliation":[{"name":"Amphastar Pharmaceuticals, Inc., Rancho Cucamonga, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward M.","family":"Kerwin","sequence":"additional","affiliation":[{"name":"Clinical Research Institute and Allergy &amp; Asthma Center, Medford, Oregon, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Don A.","family":"Bukstein","sequence":"additional","affiliation":[{"name":"Allergy, Asthma, and Sinus Center, Milwaukee, Wisconsin, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"e_1_3_5_2_2","first-page":"F5536A","volume-title":"Primatene\u00ae MIST [label]","year":"2022","unstructured":"Primatene\u00ae MIST [label]. Armstrong Pharmaceuticals, Inc., Canton, MA. 2022. p. F5536A."},{"key":"e_1_3_5_3_2","unstructured":"U.S. Food and Drug Administration. Primatene Mist with chlorofluorocarbons no longer available after Dec. 31 2011. Updated Sept. 22 2011. Available from: https:\/\/wayback.archive-it.org\/7993\/20170112011259\/http:\/www.fda.gov\/ForConsumers\/ConsumerUpdates\/ucm247196.htm [Last accessed: February16 2024]."},{"key":"e_1_3_5_4_2","unstructured":"Gottlieb S Woodcock J. FDA statement on approval of OTC Primatene Mist to treat mild asthma. Nov. 8 2018. Available from: https:\/\/www.fda.gov\/newsevents\/press-announcements\/fda-statement-approvalotc-primatene-mist-treat-mild-asthma [Last accessed: February16 2024]."},{"key":"e_1_3_5_5_2","unstructured":"Asthma and Allergy Network. FDA decision to OK Primatene Mist endangers asthma patients. Vienna Virginia; Nov. 9 2018. Available from: https:\/\/allergyasthmanetwork.org\/news\/fda-decision-approve-primatene-mist-endangers-asthma-patients\/#:\u223c:text=%E2%80%9CThe%20availability%20of%20and%20the risk%20for%20excessive%20cardiac%20stimulation.%E2%80%9D [Last accessed: March5 2024]."},{"key":"e_1_3_5_6_2","unstructured":"Asthma and Allergy Foundation of America. AAFA sign on letter to CVS urging Primatene Mist behind the counter. Jan. 25 2019. Available from: https:\/\/aafa.org\/wp-content\/uploads\/2022\/08\/aafa-sign-on-letter-to-cvs-urging-primatene-mist-behind-the-counter.pdf [Last accessed: March5 2024]."},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201902-164HP"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/WOX.0b013e318211496c"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.2147\/DHPS.S121733"},{"key":"e_1_3_5_10_2","unstructured":"National Asthma Education and Prevention Program Third Expert Panel on the Diagnosis and Management of Asthma. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Report No.:07-4051. National Heart Lung and Blood Institute (US): Bethesda (MD); 2007 Aug. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK7232\/ [Last accessed: February15 2024]."},{"key":"e_1_3_5_11_2","unstructured":"Global Initiative for Asthma. Global strategy for asthma management and prevention. 2022. 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