{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:05:02Z","timestamp":1792213502939,"version":"4.4.0"},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T00:00:00Z","timestamp":1665360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Anaphylaxis guidelines recommend intramuscular adrenaline, commonly 300\u2009\u03bcg administered using an auto\u2010injector device. However, overweight\/obese patients may require a higher adrenaline dose for adequate cardiovascular (CV) response. This study evaluated the pharmacokinetics (PK) and pharmacodynamic (PD) CV profiles after a single 500 \u03bcg adrenaline injection via Anapen auto\u2010injector in healthy normal weight males and otherwise healthy, overweight or obese females.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this exploratory open\u2010label, single\u2010centre study, 54 healthy volunteers aged 18\u201050\u2009years received a single 500 \u03bcg adrenaline injection (Anapen auto\u2010injector) in the thigh (antero\u2010lateral middle third [18 males] or antero\u2010inferior third [36 females]). Assessments included depot depth (ultrasonography), plasma adrenaline levels (liquid chromatography\u2010tandem mass spectrometry) and heart rate (HR; ECG Holter monitor).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ultrasonography showed that 82.4% of normal weight males received intramuscular injections; all overweight and obese females received subcutaneous injections. Anapen injection produced rapid increases in circulating adrenaline levels and significant increases in systolic blood pressure (SBP) and HR. Second peak plasma adrenaline concentrations (<jats:italic>C<\/jats:italic><jats:sub>max2<\/jats:sub>) were reduced, and time to <jats:italic>C<\/jats:italic><jats:sub>max2<\/jats:sub> increased in overweight and obese females compared with males with normal body mass index; area under the curve (0\u2013240 min) (AUC<jats:sub>(0\u2010240)<\/jats:sub>) was increased in overweight and obese females. Obese females had reduced maximal SBP values compared with normal weight males or overweight females; overweight and obese females had markedly different HR time courses compared with normal weight males.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A 500 \u03bcg adrenaline injection via Anapen produced rapid PK\/PD changes in normal weight, overweight and obese subjects, irrespective of intramuscular or subcutaneous injection, and was well tolerated.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15545","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T16:44:25Z","timestamp":1663865065000},"page":"1012-1019","source":"Crossref","is-referenced-by-count":9,"title":["Bioavailability and cardiovascular effects of adrenaline administered by Anapen 500\u2009\u03bcg auto\u2010injector in healthy volunteers"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4762-588X","authenticated-orcid":false,"given":"Thierry","family":"Duvauchelle","sequence":"first","affiliation":[{"name":"Bioprojet Pharma  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Robert","sequence":"additional","affiliation":[{"name":"Bioprojet Biotech  Saint Gregoire France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Donazzolo","sequence":"additional","affiliation":[{"name":"Eurofins Optimed  Gi\u00e8res France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Loyau","sequence":"additional","affiliation":[{"name":"PhinC Development  Massy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Orlandini","sequence":"additional","affiliation":[{"name":"PhinC Development  Massy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Lehert","sequence":"additional","affiliation":[{"name":"Faculty of Economics University of Louvain  Louvain Belgium"},{"name":"Faculty of Medicine University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne\u2010Marie","family":"Lecomte","sequence":"additional","affiliation":[{"name":"Bioprojet Pharma  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Charles","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Bioprojet Pharma  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199208063270603"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102222.2000.00864.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2001.112031"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12475"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.10.021"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.10.008"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.06.022"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12437"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40413\u2010015\u20100080\u20101"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2001.119409"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD008935.pub2"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2016.07.018"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2017.09.021"},{"key":"e_1_2_10_15_1","unstructured":"World Medical Association.WMA Declaration of Helsinki \u2013 Ethical Principles for Medical Research Involving Human Subjects.2013. 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