{
  "abstract": "Introduction 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 ( NCT06433908/NCT06433921) compared the pharmacokinetics (PK), pharmacodynamics (PD) and safety of salbutamol MDI with HFA-152a or HFA-134a.Methods Relative bioavailability (Study 1): healthy adults received single salbutamol doses (200/800 µg) via MDI with HFA-152a or HFA-134a. Primary PK endpoints were areas under the plasma concentration–time curve (0–30 min (AUC) 0–30 min, zero to infinity (AUC0–∞) and maximum plasma concentration (Cmax)). Relative PD potency via methacholine challenge (Study 2): patients with mild asthma received MDI placebo and salbutamol doses (100/200/400 µg) with HFA-152a or HFA-134a. The primary PD endpoint was provocative methacholine concentration (PC) causing ≥20% (PC20) forced expiratory volume in 1 s reduction.Results Study 1: 60 participants (30 per cohort) enrolled. In cohort 1 (200 µg), AUC 0–30 min was within the predefined PK bioequivalence (BE) range (0.80–1.25); in cohort 2 (800 µg), AUC0–∞ and Cmax were within the BE range. Study 2: 21 participants enrolled. PD relative potency of HFA-152a was within the predefined BE range (0.67–1.50). No serious treatment-related adverse events (AEs) were reported; all AEs were mild and occurred at similar frequencies with both propellants.Conclusions 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.",
  "authors": [
    {
      "affiliations": [
        "Clinical Pharmacology Modeling & Simulation, GSK, Collegeville, Pennsylvania, USA"
      ],
      "name": "Sebastian Moreira"
    },
    {
      "affiliations": [
        "Respiratory, Immunology & Inflammation Research Unit Medicine Development Leaders, GSK, Stevenage, UK"
      ],
      "name": "Laura Clow"
    },
    {
      "affiliations": [
        "Global Clinical Operations Development - R&D, GSK, London, UK"
      ],
      "name": "Emily Coles-Piper"
    },
    {
      "affiliations": [
        "Development Biostatistics, GSK, Upper Providence, Pennsylvania, USA"
      ],
      "name": "Alison Donald"
    },
    {
      "affiliations": [
        "Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden"
      ],
      "name": "Christer Janson"
    },
    {
      "affiliations": [
        "Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester University NHS Foundation Trust, The University of Manchester, Manchester, UK",
        "Medicines Evaluation Unit, Manchester, UK"
      ],
      "name": "Dave Singh"
    },
    {
      "affiliations": [
        "Respiratory Clinical Research Unit, GSK, Collegeville, Pennsylvania, USA"
      ],
      "name": "David Slade"
    },
    {
      "affiliations": [
        "Statistics (R&D), GSK, Bengaluru, Karnataka, India"
      ],
      "name": "Pankaj Tiwari"
    },
    {
      "affiliations": [
        "Respiratory Biostatistics, GSK, Stevenage, UK"
      ],
      "name": "Stephen Weng"
    },
    {
      "affiliations": [
        "Global Medical Affairs, General Medicines, GSK, Gold Coast, Queensland, Australia"
      ],
      "name": "Maximilian Plank"
    }
  ],
  "title": "Developing low-carbon salbutamol MDI: assessment of relative bioavailability and pharmacodynamic relative potency of salbutamol MDI with propellant HFA-152a",
  "uid": "154ff2b2-5dab-53bb-abe9-d64ac41f0b69"
}