{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:40:34Z","timestamp":1792456834106,"version":"4.5.0"},"reference-count":18,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020948","name":"AstraZeneca M\u00f6lndal","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020948","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"\n Aim<\/jats:title>\n \n Londamocitinib\u2002(AZD4604)<\/jats:ext-link>\n is an inhaled, selective\n Janus\u2002kinase\u20021\u2002(JAK1)<\/jats:ext-link>\n inhibitor in development for asthma. This open\u2010label, two\u2010part, phase I clinical study (NCT06157255) used a radiolabelled microtracer approach to evaluate the absolute bioavailability and the absorption, distribution, metabolism and excretion (ADME) of inhaled londamocitinib after intravenous and oral administration in healthy male and female participants (\n n<\/jats:italic>\n \u00a0=\u20098).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Pharmacokinetics, safety, metabolic profile and metabolite identification from plasma, urine, and faecal samples were assessed employing highly sensitive accelerator mass spectrometry. Participants received a single oral 4\u2010mg dose of [\n 14<\/jats:sup>\n C]londamocitinib (NMT 37.0\u00a0kBq [\n 14<\/jats:sup>\n C]) in Part 1 and an intravenous 30\u2010\u03bcg dose of [\n 14<\/jats:sup>\n C]londamocitinib (NMT 37.0\u00a0kBq [\n 14<\/jats:sup>\n C]), followed by a single inhaled dose of 3\u2010mg londamocitinib in Part 2.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Mean recovery of total radioactive material after oral dosing was 76.3% in faeces and 8.7% in urine. After intravenous dosing, recovery was 67.3% in faeces and 16.0% in urine. Absolute bioavailability of oral londamocitinib was 40.4% and for inhaled administration was 62.5%. Unchanged londamocitinib constituted approximately 70% of circulating radioactivity in plasma and accounted for 47.8% and 28.4% of the administered dose in excreta after oral and intravenous administration respectively. No new safety signals were observed.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Following inhaled and oral dosing, londamocitinib demonstrated rapid absorption, and faecal excretion as the principal route of elimination. Unchanged londamocitinib and metabolite M6 were the major entities present in plasma, urine and faeces. Londamocitinib, at these doses, exhibited an acceptable safety and tolerability profile.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/bcp.70844","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:30:41Z","timestamp":1792456241000},"source":"Crossref","is-referenced-by-count":0,"title":["Absorption, distribution, metabolism and excretion of londamocitinib after single\u2010dose inhaled, intravenous and oral administration in healthy participants"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3697-466X","authenticated-orcid":false,"given":"Camille","family":"Riff","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D AstraZeneca Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bold","sequence":"additional","affiliation":[{"name":"Drug Metabolism and Pharmacokinetics (DMPK), Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D AstraZeneca Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Heijer","sequence":"additional","affiliation":[{"name":"Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D AstraZeneca Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan A.","family":"Bragg","sequence":"additional","affiliation":[{"name":"Early Chemical Development, Pharmaceutical Sciences, BioPharmaceuticals R&D AstraZeneca Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Steele","sequence":"additional","affiliation":[{"name":"Early Product Development, Pharmaceutical Sciences, BioPharmaceuticals R&D AstraZeneca Macclesfield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Jellesmark Jensen","sequence":"additional","affiliation":[{"name":"Clinical Development, R&I, BioPharmaceuticals R&D AstraZeneca Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davinder P. S.","family":"Dosanjh","sequence":"additional","affiliation":[{"name":"Clinical Development, R&I, BioPharmaceuticals R&D AstraZeneca Cambridge UK"},{"name":"Birmingham Acute Care Research, Institute of Inflammation and Ageing University of Birmingham Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina I.","family":"Hanswijk\u2010Bartelds","sequence":"additional","affiliation":[{"name":"The Netherlands Organization for Applied Scientific Research (TNO) The Hague The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"van Duijn","sequence":"additional","affiliation":[{"name":"The Netherlands Organization for Applied Scientific Research (TNO) The Hague The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elwin R.","family":"Verheij","sequence":"additional","affiliation":[{"name":"The Netherlands Organization for Applied Scientific Research (TNO) The Hague The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somasekhara","family":"Menakuru","sequence":"additional","affiliation":[{"name":"Quotient Sciences Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rod","family":"Hughes","sequence":"additional","affiliation":[{"name":"Clinical Development, R&I, BioPharmaceuticals R&D AstraZeneca Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Dahlb\u00e4ck","sequence":"additional","affiliation":[{"name":"Drug Metabolism and Pharmacokinetics (DMPK), Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D AstraZeneca Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2025.12.1008"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c00554"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931\u2010025\u201003309\u20103"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjresp\u20102025\u2010003589"},{"key":"e_1_2_11_6_1","unstructured":"US Food and Drug Administration.2024.Clinical Pharmacology Considerations for Human Radiolabeled Mass Balance Studies. 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