ACUTE SAFETY OF THE CFC-FREE PROPELLANT HFA-134A FROM A PRESSURIZED METERED-DOSE INHALER

The acute safety of the alternative chlorofluorocarbon-free (CFC-free) propellant HFA-134a from a pressurized metered-dose inhaler (MDI) was assessed in 12 healthy male subjects according to a double-blind, ran domized, crossover design. On each of three consecutive days, cumulati ve doses of 1, 2, 4, 8 and 16 inhalations were administered 30 min apa rt from one of three MDIs. The three MDIs contained either the HFA-134 a CFC-free system without drug (HFA-Placebo), the CFC-free system with salbutamol sulphate (HFA-Salbutamol), or a conventional CFC propellan t mixture without drug (CFC-Placebo). Pulmonary function (FEV(1), FEF( 25-75%)), cardiovascular performance (heart rate and blood pressure), objective tremor measurements and serum potassium were measured after each incremental dose. Similar responses for pulmonary function, cardi ovascular performance, tremor and serum potassium were observed betwee n the HFA-Placebo and CFC-Placebo groups. No statistically significant difference was seen in change from baseline of any parameter between the two propellant systems. The administration of HFA-Salbutamol produ ced statistically significant dose-related increases in heart rate, sy stolic blood pressure and tremor and a significant dose-related decrea se in serum potassium; these responses were expected based on cumulati ve doses of active drug. Blood samples for HFA-134a analysis were coll ected to measure systemic absorption of this propellant. Levels of HFA -134a between 200 and 700 ng . ml(-1) were detected in all subjects gi ven the CFC-free system. This study shows that acute inhalation of HFA -134a in a CFC-free system is as safe as a CFC propellant system. Salb utamol sulphate in the CFC-free system can be delivered in a dose-line ar fashion, without any noticeable change in the safety profile of act ive drug.