Abstract

HFA134a (1,1,1,2-tetrafluoroethane) is a nonozone-depleting candidate to replace the chlorofluorocarbons used as propellants in metered-dose inhalers (MDIs) for pharmaceuticals that are widely used in the treatment of respiratory tract disease. As a means for ensuring the safety of such a compound for human use, it is necessary to establish that there is no excessive or unexpected accumulation in the body and in selected regions. A sensitive whole-body gamma-counting technique has been used with 18F-labeled HFA134a to measure the whole-body and regional absorption, distribution, and retention of HFA134a after administration in humans by single-breath inhalation. In seven healthy subjects, labeled HFA134a was rapidly eliminated by ventilation during the first few minutes, with an average of 9.6% of the radioactivity retained in the body at 5 min. This radioactivity cleared with an apparent terminal half-life of 1.5-4.2 hr to leave, on average, < 1% of the administered dose (< 750 micrograms, approximately 0.2 microCi) retained in the body at 5.8 hr. Disposition of radioactivity was independent of the position of label. Thus, there was no evidence of any significant degradative metabolism. On average, only 0.0056% of the administered dose appeared in the urine within the first 2 hr. Later samples contained no significant radioactivity. Inhaled HFA134a first distributed to all regions of the body and then cleared without evident accumulation in any specific region.(ABSTRACT TRUNCATED AT 250 WORDS)