{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T10:23:05Z","timestamp":1787307785767,"version":"build-2736575974"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"STIMAG","award":["2022"],"award-info":[{"award-number":["2022"]}]},{"name":"STIMAG"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>An adrenal crisis is a potentially life-threatening medical emergency that requires rapid treatment with glucocorticoids. Guidelines advise immediate self-administration of hydrocortisone by intramuscular injection using an emergency management kit in case an adrenal crisis is suspected. However, self-injection is often not performed due to administration complexity or patient anxiety. Pulmonary administration of glucocorticoids may be a more patient-friendly and suitable alternative, especially when administered using a dry powder inhaler. Before advancing to the development of a dry powder inhaler, we aimed to evaluate whether the pharmacokinetics of inhaled prednisolone sodium succinate are suitable for the outpatient treatment of adrenal crisis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twelve healthy participants (aged 23-31 years, 50% females) received 2 separate doses of prednisolone sodium succinate, equivalent to 56.1 and 112.2\u2005mg prednisolone on separate occasions, administered via a nebulizer. The primary outcome was the time to reach a target plasma concentration of 200\u2005nmol\/L.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The median times to achieve this plasma concentration (excluding the nebulization time of approximately 10\u2005minutes) were 17 (13-23) minutes and 9 (5-11) minutes for the 56.1 and 112.2\u2005mg doses, respectively. Furthermore, pulmonary-administered prednisolone sodium succinate was well tolerated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The results of this study, particularly the short time to the target plasma concentration, indicate that prednisolone sodium succinate is rapidly absorbed via the lungs and that the pharmacokinetics of inhaled nebulized prednisolone sodium succinate are suitable for the outpatient treatment of adrenal crisis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvag143","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:23:44Z","timestamp":1785756224000},"page":"312-319","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics of inhaled prednisolone for adrenal crisis: an exploratory study"],"prefix":"10.1093","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1675-562X","authenticated-orcid":false,"given":"Julia M E","family":"Berends","sequence":"first","affiliation":[{"name":"Faculty of Science and Engineering, Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, University of Groningen , Antonius Deusinglaan 1, 9713 AV Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annet","family":"Vulto","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Medical Center Groningen, University of Groningen , PO Box 30001, 9700 RB Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascalle A","family":"van den Wijngaard","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Medical Center Groningen, University of Groningen , PO Box 30001, 9700 RB Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9379-2219","authenticated-orcid":false,"given":"Michel J","family":"Vos","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen , PO Box 30001, 9700 RB Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daan J","family":"Touw","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen , PO Box 30001, 9700 RB Groningen ,","place":["The Netherlands"]},{"name":"Faculty of Science and Engineering, Department of Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen , Antonius Deusinglaan 1, 9713 AV Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henderik W","family":"Frijlink","sequence":"additional","affiliation":[{"name":"Faculty of Science and Engineering, Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, University of Groningen , Antonius Deusinglaan 1, 9713 AV Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0335-8177","authenticated-orcid":false,"given":"Andr\u00e9 P","family":"van Beek","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Medical Center Groningen, University of Groningen , PO Box 30001, 9700 RB Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"issue":"1","key":"2026082105262128300_lvag143-B1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1111\/cen.12865","article-title":"Incidence of adrenal crisis in patients with adrenal insufficiency","volume":"84","author":"Smans","year":"2016","journal-title":"Clin Endocrinol"},{"issue":"3","key":"2026082105262128300_lvag143-B2","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1530\/EJE-09-0884","article-title":"Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies","volume":"162","author":"Hahner","year":"2010","journal-title":"Eur J Endocrinol"},{"issue":"2","key":"2026082105262128300_lvag143-B3","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1210\/jc.2014-3191","article-title":"High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study","volume":"100","author":"Hahner","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2026082105262128300_lvag143-B4","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1007\/s12020-017-1513-0","article-title":"Longitudinal AddiQoL scores may identify higher risk for adrenal crises in Addison's disease","volume":"60","author":"Meyer","year":"2018","journal-title":"Endocrine"},{"issue":"1","key":"2026082105262128300_lvag143-B5","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1055\/a-2130-1938","article-title":"Adrenal crisis\u2014definition, prevention and treatment: results from a Delphi survey","volume":"56","author":"Kienitz","year":"2024","journal-title":"Horm Metab Res"},{"issue":"2","key":"2026082105262128300_lvag143-B6","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1210\/jc.2015-1710","article-title":"Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society Clinical Practice guideline","volume":"101","author":"Bornstein","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"2026082105262128300_lvag143-B7","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1007\/s12020-021-02649-6","article-title":"Therapy options for adrenal insufficiency and recommendations for the management of adrenal crisis","volume":"71","author":"Nowotny","year":"2021","journal-title":"Endocrine"},{"issue":"1","key":"2026082105262128300_lvag143-B8","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1530\/EJE-09-0559","article-title":"Adrenal crisis in treated Addison's disease: a predictable but under-managed event","volume":"162","author":"White","year":"2010","journal-title":"Eur J Endocrinol"},{"key":"2026082105262128300_lvag143-B9","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.849188","article-title":"Susceptibility to adrenal crisis is associated with differences in cortisol excretion in patients with secondary adrenal insufficiency","volume":"13","author":"Vulto","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"2026082105262128300_lvag143-B10","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1111\/cen.13608","article-title":"Management of adrenal emergencies in educated patients with adrenal insufficiency\u2014a prospective study","volume":"89","author":"Burger-Stritt","year":"2018","journal-title":"ClinEndocrinol"},{"key":"2026082105262128300_lvag143-B11","doi-asserted-by":"publisher","DOI":"10.1177\/2042018819848218","article-title":"Adrenal crisis: prevention and management in adult patients","volume":"10","author":"Dineen","year":"2019","journal-title":"Ther Adv Endocrinol Metab"},{"key":"2026082105262128300_lvag143-B12","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1544502","article-title":"Patient and caregiver experiences with hydrocortisone injections in adrenal crisis: a mixed-methods cross-sectional study","volume":"16","author":"Llahana","year":"2025","journal-title":"Front Endocrinol"},{"issue":"4","key":"2026082105262128300_lvag143-B13","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1513\/pats.200409-049TA","article-title":"The lungs as a portal of entry for systemic drug delivery","volume":"1","author":"Patton","year":"2004","journal-title":"Proc Am Thorac Soc."},{"issue":"1","key":"2026082105262128300_lvag143-B14","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1192\/bjp.bp.110.081513","article-title":"Rapid acute treatment of agitation in individuals with schizophrenia: multicentre, randomised, placebo-controlled study of inhaled loxapine","volume":"198","author":"Lesem","year":"2011","journal-title":"Br J Psychiatry"},{"issue":"9","key":"2026082105262128300_lvag143-B15","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1002\/mds.26611","article-title":"A randomized trial of inhaled levodopa (CVT-301) for motor fluctuations in Parkinson's disease","volume":"31","author":"LeWitt","year":"2016","journal-title":"Mov Disord"},{"key":"2026082105262128300_lvag143-B16","doi-asserted-by":"publisher","DOI":"10.1177\/2040622319857617","article-title":"Pharmacokinetics and tolerability of inhaled levodopa from a new dry-powder inhaler in patients with Parkinson's disease","volume":"10","author":"Luinstra","year":"2019","journal-title":"Ther Adv Chronic Dis"},{"issue":"1","key":"2026082105262128300_lvag143-B17","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.ijpharm.2018.07.008","article-title":"Challenges for pulmonary delivery of high powder doses","volume":"548","author":"Sibum","year":"2018","journal-title":"Int J Pharm"},{"key":"2026082105262128300_lvag143-B18","author":"European Medicines Agency"},{"issue":"1","key":"2026082105262128300_lvag143-B19","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jcf.2010.08.019","article-title":"Lung deposition of inhaled tobramycin with eFlow rapid\/LC Plus jet nebuliser in healthy and cystic fibrosis subjects","volume":"10","author":"Lenney","year":"2011","journal-title":"J Cyst Fibros."},{"issue":"5","key":"2026082105262128300_lvag143-B20","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1111\/cen.13820","article-title":"The cortisol stress response induced by surgery: a systematic review and meta-analysis","volume":"89","author":"Prete","year":"2018","journal-title":"Clin Endocrinol"},{"key":"2026082105262128300_lvag143-B21","author":"National Institute for Health and Care Excellence"},{"issue":"11","key":"2026082105262128300_lvag143-B22","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1016\/s0006-3223(01)01314-2","article-title":"A novel prednisolone suppression test for the hypothalamic-pituitary-adrenal axis","volume":"51","author":"Pariante","year":"2002","journal-title":"Biol Psychiatry"},{"issue":"2","key":"2026082105262128300_lvag143-B23","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1530\/EJE-12-1057","article-title":"Subcutaneous hydrocortisone administration for emergency use in adrenal insufficiency","volume":"169","author":"Hahner","year":"2013","journal-title":"Eur J Endocrinol"},{"key":"2026082105262128300_lvag143-B24","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.metabol.2017.02.005","article-title":"Pharmacokinetics of oral hydrocortisone\u2014results and implications from a randomized controlled trial","volume":"71","author":"Werumeus Buning","year":"2017","journal-title":"Metabolism"},{"issue":"1","key":"2026082105262128300_lvag143-B25","doi-asserted-by":"publisher","first-page":"61","DOI":"10.2165\/00003088-200544010-00003","article-title":"Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids","volume":"44","author":"Czock","year":"2005","journal-title":"Clin Pharmacokinet"},{"key":"2026082105262128300_lvag143-B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neuroscience.2011.02.053","article-title":"New insights into corticosteroid-binding globulin and glucocorticoid delivery","volume":"180","author":"Henley","year":"2011","journal-title":"Neuroscience"},{"issue":"6","key":"2026082105262128300_lvag143-B27","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1089\/jamp.2010.0816","article-title":"Delivery efficacy of a vibrating mesh nebulizer and a jet nebulizer under different configurations","volume":"23","author":"Pitance","year":"2010","journal-title":"J Aerosol Med Pulm Drug Deliv"},{"key":"2026082105262128300_lvag143-B28","volume-title":"Endotext","author":"Nicolaides","year":"2018"},{"issue":"10","key":"2026082105262128300_lvag143-B29","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1002\/jps.2600751004","article-title":"Oral absorption of 21-corticosteroid esters: a function of aqueous stability and intestinal enzyme activity and distribution","volume":"75","author":"Fleisher","year":"1986","journal-title":"J Pharm Sci."}],"container-title":["European Journal of Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ejendo\/advance-article-pdf\/doi\/10.1093\/ejendo\/lvag143\/70478233\/lvag143.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/195\/2\/312\/70478233\/lvag143.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/195\/2\/312\/70478233\/lvag143.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T09:26:30Z","timestamp":1787304390000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/195\/2\/312\/8750877"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,8,3]]}},"URL":"https:\/\/doi.org\/10.1093\/ejendo\/lvag143","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,8]]}}}