{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T06:32:30Z","timestamp":1793514750199,"version":"4.5.0"},"reference-count":32,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"unspecified","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"GSK","award":["219728\/219729"],"award-info":[{"award-number":["219728\/219729"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Resp Res"],"accepted":{"date-parts":[[2026,4,30]]},"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Climate change is a global threat. Propellant hydrofluoroalkane (HFA)-134a in metered-dose inhalers (MDIs) contributes to healthcare-related greenhouse gas emissions. HFA-152a is a new propellant with ~90% lower global warming potential than HFA-134a. Two phase I studies (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06433908\">NCT06433908<\/jats:ext-link>\n                      \/NCT06433921) compared the pharmacokinetics (PK), pharmacodynamics (PD) and safety of salbutamol MDI with HFA-152a or HFA-134a.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Relative bioavailability (Study 1): healthy adults received single salbutamol doses (200\/800\u2009\u00b5g) via MDI with HFA-152a or HFA-134a. Primary PK endpoints were areas under the plasma concentration\u2013time curve (0\u201330\u2009min (AUC)\n                      <jats:sub>0\u201330 min<\/jats:sub>\n                      , zero to infinity (AUC\n                      <jats:sub>0\u2013\u221e<\/jats:sub>\n                      ) and maximum plasma concentration (C\n                      <jats:sub>max<\/jats:sub>\n                      )). Relative PD potency via methacholine challenge (Study 2): patients with mild asthma received MDI placebo and salbutamol doses (100\/200\/400\u2009\u00b5g) with HFA-152a or HFA-134a. The primary PD endpoint was provocative methacholine concentration (PC) causing \u226520% (PC\n                      <jats:sub>20<\/jats:sub>\n                      ) forced expiratory volume in 1\u2009s reduction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Study 1: 60 participants (30 per cohort) enrolled. In cohort 1 (200 \u00b5g), AUC\n                      <jats:sub>0\u201330 min<\/jats:sub>\n                      was within the predefined PK bioequivalence (BE) range (0.80\u20131.25); in cohort 2 (800 \u00b5g), AUC\n                      <jats:sub>0\u2013\u221e<\/jats:sub>\n                      and C\n                      <jats:sub>max<\/jats:sub>\n                      were within the BE range. Study 2: 21 participants enrolled. PD relative potency of HFA-152a was within the predefined BE range (0.67\u20131.50). No serious treatment-related adverse events (AEs) were reported; all AEs were mild and occurred at similar frequencies with both propellants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Salbutamol with HFA-152a demonstrated equivalence in key PK and PD parameters, as well as a similar safety profile to salbutamol with HFA-134a, supporting salbutamol MDI with HFA-152a as a therapeutically equivalent, low-carbon replacement.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjresp-2025-004036","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T15:10:12Z","timestamp":1781709012000},"page":"e004036","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Developing low-carbon salbutamol MDI: assessment of relative bioavailability and pharmacodynamic relative potency of salbutamol MDI with propellant HFA-152a"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct06433908","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06261957","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06433908","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06433921","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7316-2558","authenticated-orcid":false,"given":"Sebastian","family":"Moreira","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Modeling & Simulation, GSK, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Clow","sequence":"additional","affiliation":[{"name":"Respiratory, Immunology & Inflammation Research Unit Medicine Development Leaders, GSK, Stevenage, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Coles-Piper","sequence":"additional","affiliation":[{"name":"Global Clinical Operations Development - R&D, GSK, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Donald","sequence":"additional","affiliation":[{"name":"Development Biostatistics, GSK, Upper Providence, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5093-6980","authenticated-orcid":false,"given":"Christer","family":"Janson","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave","family":"Singh","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester University NHS Foundation Trust, The University of Manchester, Manchester, UK"},{"name":"Medicines Evaluation Unit, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Slade","sequence":"additional","affiliation":[{"name":"Respiratory Clinical Research Unit, GSK, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Statistics (R&D), GSK, Bengaluru, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Weng","sequence":"additional","affiliation":[{"name":"Respiratory Biostatistics, GSK, Stevenage, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Plank","sequence":"additional","affiliation":[{"name":"Global Medical Affairs, General Medicines, GSK, Gold Coast, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"2026061708100656000_13.1.e004036.1","unstructured":"World Health Organization . 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