{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T11:55:08Z","timestamp":1764330908412},"reference-count":10,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,7,8]],"date-time":"2016-07-08T00:00:00Z","timestamp":1467936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>AZD5423 is a selective glucocorticosteroid receptor modulator developed for the inhaled use in asthma and <jats:styled-content style=\"fixed-case\">COPD<\/jats:styled-content>. This study reports the initial, first\u2010in\u2010man, single and repeat dose\u2010escalating studies in healthy male individuals, including one cohort of male Japanese individuals. Inhaled, nebulized <jats:styled-content style=\"fixed-case\">AZD<\/jats:styled-content>5423 was safe and well tolerated up to and including the highest doses tested for up to 2 weeks of once\u2010daily treatment. Plasma exposure suggested dose\u2010proportional pharmacokinetics and dose\u2010related effects on 24\u2010hr plasma and urine cortisol. There were no or marginal effects on other biomarkers tested (osteocalcin, <jats:styled-content style=\"fixed-case\">TRAP<\/jats:styled-content>5b, <jats:styled-content style=\"fixed-case\">DHEA<\/jats:styled-content>\u2010S and 4\u03b2\u2010<jats:styled-content style=\"fixed-case\">OH<\/jats:styled-content>\u2010cholesterol). No clinically relevant differences in safety or pharmacokinetics could be distinguished between the two study populations, although hypothalamus\u2013pituitary\u2013adrenal (<jats:styled-content style=\"fixed-case\">HPA<\/jats:styled-content>) effects appeared to be marginally greater in the Japanese\u2010 <jats:italic>versus<\/jats:italic> the Caucasian\u2010dominant study population. <jats:styled-content style=\"fixed-case\">AZD<\/jats:styled-content>5423, inhaled via nebulization, can be used in healthy individuals at doses of at least 300 \u03bcg for 2 weeks. The effects on the <jats:styled-content style=\"fixed-case\">HPA<\/jats:styled-content> axis reported herein, together with efficacy data reported elsewhere, indicate that benefit\u2013risk ratio may be improved relative to conventional inhaled steroids.<\/jats:p>","DOI":"10.1111\/bcpt.12621","type":"journal-article","created":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T10:43:05Z","timestamp":1464086585000},"page":"574-581","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Safety, Pharmacokinetics and Pharmacodynamics of the Selective Glucocorticoid Receptor Modulator AZD5423 after Inhalation in Healthy Volunteers"],"prefix":"10.1111","volume":"119","author":[{"given":"Viktoria","family":"Werkstr\u00f6m","sequence":"first","affiliation":[{"name":"AstraZeneca Global Medicines Development Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Prothon","sequence":"additional","affiliation":[{"name":"AstraZeneca Global Medicines Development Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ella","family":"Ekholm","sequence":"additional","affiliation":[{"name":"AstraZeneca Global Medicines Development Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carin","family":"Jorup","sequence":"additional","affiliation":[{"name":"AstraZeneca Global Medicines Development Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Staffan","family":"Edsb\u00e4cker","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Pharmacology Laboratory Medicines Unit Lund University Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,7,8]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"HanssonT BergerM Dahm\u00e9nJ EdmanK ErikssonA GabosBet al.Discovery of AZD5423 a potent and selective non\u2010steroidal glucocorticoid receptor modulator for the inhaled treatment of respiratory diseases [abstract MEDI\u2010278]. Presented at 245th National Meeting of the American Chemical Society New Orleans LA; April 7\u201311 2013."},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2014.03.070"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201404-0623OC"},{"key":"e_1_2_6_5_1","article-title":"Pharmacokinetics of an inhaled selective glucocorticoid receptor modulator following inhalation using different devices","author":"Melin J","year":"2016","journal-title":"Br J Clin Pharmacol"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/jamp.2016.1306"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)03339-9"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.159.9.941"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-12-160"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aller.2010.06.005"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050287"}],"container-title":["Basic &amp; Clinical Pharmacology &amp; Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcpt.12621","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcpt.12621","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.12621","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T12:57:52Z","timestamp":1695733072000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcpt.12621"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,8]]},"references-count":10,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["10.1111\/bcpt.12621"],"URL":"https:\/\/doi.org\/10.1111\/bcpt.12621","archive":["Portico"],"relation":{},"ISSN":["1742-7835","1742-7843"],"issn-type":[{"value":"1742-7835","type":"print"},{"value":"1742-7843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,8]]},"assertion":[{"value":"2016-02-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-05-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-07-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}