{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T15:31:13Z","timestamp":1777908673893,"version":"3.51.4"},"reference-count":12,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"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":[[2020,10,1]]},"abstract":"\n \n Background<\/jats:italic>\n :\n <\/jats:title>\n \n Primatene\n \u00ae<\/jats:sup>\n MIST CFC, an epinephrine metered-dose inhaler (MDI), was discontinued from the market owing to environmental concerns from its use of chlorofluorocarbon (CFC) propellant. As a result, a new epinephrine MDI was developed using hydrofluoroalkane (HFA) propellant. This article reports the pharmacokinetic (PK) profile of the newly Food and Drug Administration-approved epinephrine HFA MDI.\n <\/jats:p>\n <\/jats:sec>\n \n \n Methods<\/jats:italic>\n :\n <\/jats:title>\n \n A randomized, evaluator-blinded, active-controlled, single-dose, two-arm crossover study was conducted to evaluate the PK profile of epinephrine HFA (Primatene\n \u00ae<\/jats:sup>\n MIST) and epinephrine CFC (Primatene\n \u00ae<\/jats:sup>\n MIST CFC) in 23 healthy volunteers to characterize the epinephrine absorption extent and rate. The study was performed at a high dose of five times the normal dose to obtain measurable plasma epinephrine levels. Plasma epinephrine levels were measured and safety was assessed by adverse events (AEs), vital signs, clinical laboratory tests, and physical examinations.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n : Epinephrine HFA demonstrated a greater systemic drug exposure (greater area under the curve) than that of epinephrine CFC (\u223c37% higher). The\n C<\/jats:italic>\n max<\/jats:sub>\n occurred at \u223c2 minutes and was significantly higher in the epinephrine HFA group (0.18\u2009ng\/mL) compared with the CFC version (0.046\u2009ng\/mL) at normal dose. Within 20 minutes, both groups demonstrated comparable plasma epinephrine levels. No clinically significant adverse effects were found to be associated with epinephrine HFA, even after an ultrahigh dose (i.e., 10 inhalations).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n The systemic exposure of epinephrine HFA was found to be higher for the first 20 minutes, and then comparable with epinephrine CFC. Minimal AEs were found in this study despite the very high 1250\u20132200\u2009\u03bcg inhaled doses (i.e., 10 inhalations) used for PK characterization.<\/jats:p>\n <\/jats:sec>","DOI":"10.1089\/jamp.2019.1577","type":"journal-article","created":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T01:29:18Z","timestamp":1589851758000},"page":"282-287","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetic Study of Epinephrine Hydrofluoroalkane (Primatene MIST) Metered-Dose Inhaler"],"prefix":"10.1177","volume":"33","author":[{"given":"Edward M.","family":"Kerwin","sequence":"first","affiliation":[{"name":"Clinical Research Institute of Southern Oregon, Medford, Oregon, 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":"Mary Z.","family":"Luo","sequence":"additional","affiliation":[{"name":"Amphastar Pharmaceuticals, Inc., Rancho Cucamonga, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack Y.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Amphastar Pharmaceuticals, Inc., Rancho Cucamonga, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2020,9,30]]},"reference":[{"key":"e_1_3_3_2_2","unstructured":"Federal Register Volume 73 no 224: 21 CFR part 2: Use of ozone-depleting substances; removal of essential-use designation (Epinephrine) final rule. November 19 2008."},{"key":"e_1_3_3_3_2","unstructured":"Gao J Luo J Zhou R Luo MZ and Zhang JY: Stable epinephrine suspension formulation with high inhalation delivery efficiency. US Patent 8 367 734 B1. February 5 2013. Available from: https:\/\/patentimages.storage.googleapis.com\/67\/65\/d4\/461c6f9a24c31a\/US8367734.pdf (Accessed on December18 2019)."},{"key":"e_1_3_3_4_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. Bethesda (MD): National Heart Lung and Blood Institute (US); 2007 Aug. Report No.:07-4051. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK72321\/ [Last accessed September9 2015]."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00117"},{"key":"e_1_3_3_6_2","volume-title":"Basic and Clinical Pharmacology","author":"Katzung B","year":"2004","unstructured":"Katzung B: Basic and Clinical Pharmacology. 9th ed. 2004. New York: Lange Medical Books\/McGraw\/Hill.","edition":"9"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1986.61.5.1693"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1986.243"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1081-1206(10)61014-9"},{"key":"#cr-split#-e_1_3_3_10_2.1","unstructured":"FDA Briefing Document for a Joint Meeting of the Nonprescription Drugs and the Pulmonary and Allergy Drugs Advisory Committees. Risk\/benefit considerations for use of epinephrine as an OTC asthma therapy. Silver Spring MD February 25 2014"},{"key":"#cr-split#-e_1_3_3_10_2.2","unstructured":"pp. 51-52. Available from: http:\/\/wayback.archive-it.org\/7993\/20170113233021\/http:\/\/www.fda.gov\/downloads\/AdvisoryCommittees\/CommitteesMeetingMaterials\/Drugs\/NonprescriptionDrugsAdvisoryCommittee\/UCM386675.pdf (Accessed on January28 2019)."},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2001.119409"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.5847\/wjem.j.issn.1920-8642.2013.04.001"}],"container-title":["Journal of Aerosol Medicine and Pulmonary Drug Delivery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/jamp.2019.1577","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/jamp.2019.1577","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/jamp.2019.1577","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T14:10:44Z","timestamp":1777644644000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/jamp.2019.1577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,30]]},"references-count":12,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,10,1]]}},"alternative-id":["10.1089\/jamp.2019.1577"],"URL":"https:\/\/doi.org\/10.1089\/jamp.2019.1577","relation":{},"ISSN":["1941-2711","1941-2703"],"issn-type":[{"value":"1941-2711","type":"print"},{"value":"1941-2703","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,30]]}}}