The Disposition of a New Drug Propellant (HFA 134a) in Humans Studied by Fluorine-18 Labelling and Whole-Body γ-Counting

HFA 134a (1,1,1,2-tetrafluoroethane) is a ‘non-ozone depleting’ candidate for use as a drug propellant in multi-dose inhalers (MDIs). A means for assuring the safety of such a compound for human use is to check mat there is no excessive or unexpected accumulation in the body and selected regions. HFA 134a has been labelled with fluorine-18 and used with a highly sensitive whole-body γ-counting technique to measure the whole-body and regional absorption, distribution and retention of HFA 134a after administration in humans by single breath inhalation. In 7 healthy subjects, radiolabeled HFA 134a was mainly eliminated by ventilation during the first few minutes, with on average 7.2% of the radioactivity retained in the body at 10 min. This radioactivity cleared with an apparent terminal half-life of 1.5-4.2 h. At 5.5 h an average of < 1% of the administered dose (< 750 μg, ca 0.2 μCi) was retained in the body. The disposition of radioactivity was independent of the position of radiolabel. Hence, there was no evidence of degradative metabolism. Inhaled HFA 134a first distributed to all regions of the body and then cleared without evident accumulation in any specific region. The study supports the proposal that HFA 134a is a safe substitute for current propellants in MDIs.