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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.