{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:59:57Z","timestamp":1785373197270,"version":"3.55.0"},"reference-count":20,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T00:00:00Z","timestamp":1775260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T00:00:00Z","timestamp":1775260800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To develop and validate a physiologically\u2010based pharmacokinetic (PBPK) model enabling inhaled oxytocin dose selection for clinical evaluation. Subsequently, to conduct a phase 1 study investigating the pharmacokinetics and safety of selected doses of an optimized inhaled oxytocin product in healthy, non\u2010pregnant female participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>A general PBPK model for inhaled oxytocin in non\u2010pregnant female participants was developed with the ability to estimate clinical exposure for new devices and deposition characteristics. This was used to select the oxytocin dose range for a randomized, single\u2010centre, partially single\u2010blind, placebo\u2010controlled, fixed\u2010sequence phase 1 study in comparison to standard of care injectable doses in a part cross\u2010over design. Participants received increasing inhaled oxytocin doses (150\u2009\u03bcg, 300\u2009\u03bcg, 600\u2009\u03bcg and 900\u2009\u03bcg) in single and\/or repeat dose regimens. The primary endpoints were pharmacokinetic characteristics and local tolerability following inhaled dosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifteen of 20 randomized participants completed the study. The pharmacokinetics following inhaled oxytocin administration were consistent with intramuscular dosing with the 150\u2009\u03bcg (C\n                      <jats:sub>max<\/jats:sub>\n                      \u2009=\u200977\u2009pg\/mL, AUC\n                      <jats:sub>0\u2010inf<\/jats:sub>\n                      \u2009=\u20092488\u2009min.pg\/mL) and 600\u2009\u03bcg (C\n                      <jats:sub>max<\/jats:sub>\n                      \u2009=\u2009398\u2009pg\/mL, AUC\n                      <jats:sub>0\u2010inf<\/jats:sub>\n                      \u2009=\u200914\u2009792\u2009min.pg\/mL) inhaled oxytocin doses bracketing the 10\u2009IU intramuscular doses (C\n                      <jats:sub>max<\/jats:sub>\n                      \u2009=\u2009197\u2009pg\/mL, AUC\n                      <jats:sub>0\u2010inf<\/jats:sub>\n                      \u2009=\u20098560\u2009min.pg\/mL). Repeat dosing of inhaled oxytocin was well\u2010tolerated, and no significant treatment\u2010related adverse events or clinical findings were reported. The PBPK model accurately predicted key PK parameters within two\u2010fold of the observed values.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Further development of inhaled oxytocin as an innovative product to address preventable postpartum haemorrhage in low\u2010resource settings is warranted.<\/jats:p>\n                    <jats:p>Trial registration: Australia New Zealand Clinical Trial Registry (ACTRN12622001077752p) registered 04\/08\/2022.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70544","type":"journal-article","created":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T08:36:16Z","timestamp":1775291776000},"page":"2672-2681","source":"Crossref","is-referenced-by-count":0,"title":["A phase 1 evaluation of inhaled oxytocin: Physiologically\u2010based pharmacokinetic model informed dosing of a novel heat\u2010stable oxytocin delivery system"],"prefix":"10.1002","volume":"92","author":[{"given":"Pete","family":"Lambert","sequence":"first","affiliation":[{"name":"Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences Monash University  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5715-1534","authenticated-orcid":false,"given":"Carl M. 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