DISPOSITION OF INHALED 1,1,1,2-TETRAFLUOROETHANE (HFA134A) IN HEALTHY-SUBJECTS AND IN PATIENTS WITH CHRONIC AIR-FLOW LIMITATION - MEASUREMENT BY F-18 LABELING AND WHOLE-BODY GAMMA-COUNTING

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 treat ment of respiratory tract disease. As a means for ensuring the safety of such a compound for human use, it is necessary to establish that th ere is no excessive or unexpected accumulation in the body and in sele cted regions. A sensitive whole-body gamma-counting technique has been used with F-18-labeled HFA134a to measure the whole-body and regional absorption, distribution, and retention of HFA134a after administrati on in humans by single-breath inhalation. In seven healthy subjects, l abeled 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 termina l half-life of 1.5-4.2 hr to leave, on average, <1% of the administere d dose (<750 mu g, similar to 0.2 mu Ci) retained in the body at 5.8 h r. Disposition of radioactivity was independent of the position of lab el. Thus, there was no evidence of any significant degradative metabol ism. On average, only 0.0056% of the administered dose appeared in the urine within the first 2 hr, Later samples contained no significant r adioactivity. Inhaled HFA134a first distributed to all regions of the body and then cleared without evident accumulation in any specific reg ion. In four patients with chronic airflow limitation, the pharmacokin etics of labeled HFA134a was very similar to those in healthy subjects , except that the whole-body retention of radioactivity was on average slightly greater (15.4% at 5 min after inhalation) because of the sub stantially reduced ventilatory efficiency of these severe patients. By demonstrating that HFA134a is cleared rapidly and is not retained nor metabolized to a significant extent, the study supports the proposal that this compound is a safe substitute for current propellants in MDI s.