Pharmacokinetic Analysis of Aerosol Propellant HFA‐134a Elimination in the Human Breath

Abstract

The goal of the study is to model the elimination kinetics of Hydrofluoroalkane (HFA‐134a) in the exhaled breath following a typical single asthma inhaler administration. HFA‐134a is the most commonly used aerosol propellant in metered dose inhalers. We previously demonstrated that our technical capabilities allow us to measure breath HFA‐134a levels at 24 to 48 hours post asthma inhaler administration, and thus breath HFA‐134a is a promising biomarker for identifying asthma inhaler compliance (Clinical and Translational Science 2015).Exhaled breath gases were collected in evacuated electro‐polished stainless steel canisters from healthy participants at baseline and at 5 min, 7 min, 10 min, 15 min, 30 min, 1hr, 2hr, 3hr, 4hr, 6hr, 8hr, 12hr. 24hr, 36hr, and 48hr ‐post inhaled corticosteroids administration (Flovent HFA, Glaxo Smith Kline). The corresponding ambient HFA‐134a levels were also measured. HFA‐134a levels in the breath and ambient air samples were quantified using gas chromatography with a quadrupole mass spectrometer detector. The Institutional Review Board at the University of California, Irvine approved the study, and informed consent was obtained from the participants.HFA elimination in the breath followed a three‐exponential pharmacokinetic model. The estimated time constants (mean (SD)) for the three components were 5.5 (0.5) minutes, 62.4 (11.1) minutes, and 664 (140) minutes, with an overall mean retention time (MRT) of 71.8 (40.4) minutes. The shortest and longest half‐life components comprised 66 (17) % and 9 (7) % of the total area under the curve, respectively. Breath carbon dioxide (CO2) levels were also monitored as a reference breath gas to ensure that the gas sampled was alveolar gas. The mean (SD) CO2 level was 4.7 (0.6) % of all breath samples.This study demonstrates that the breath HFA‐134a elimination in healthy control humans can be described by a 3rd order exponential equation. In earlier studies, we modeled bicarbonate distribution kinetics and found similar time constants (2.2 min, 11.9 min, and 83.3 min; MRT 65 min.; Barstow et al. Am. J. Physiol. 259: R163, 1990). We speculate that the first two time constants reflect compartmental kinetics with the lung and circulation while the slowest primarily reflects distribution to body tissues. The kinetics for HFA‐134a appear to be slower than for bicarbonate. The calculated HFA‐134a elimination parameters (i.e., rate constants or corresponding half‐lives) may be useful in conjunction with breath HFA‐134a levels for accessing asthma inhaler medication compliance and further to understand physiological complexity of the lungs that affect HFA‐134a elimination.Support or Funding InformationThis work was supported by NIH grants: Translational Pilot Research Award (subaward of UL1 TR000153) and Program Project Grant P01HD048721