Relative Lung and Systemic Bioavailability Along with Oropharyngeal Deposition of Salbutamol Post-Inhalation: A Pharmacokinetic Evaluation of Novel Inhaler Technique Training Gadgets

J Aerosol Med Pulm Drug Deliv. 2022 Oct;35(5):278-285. doi: 10.1089/jamp.2022.0006. Epub 2022 Aug 18.


Background: Suboptimal use of pressurized metered dose inhaler (pMDI) remains a major barrier to inhaled therapy success. Verbal inhaler technique training (VT) fails to maintain patients' good pMDI use, thus training tools might help. Trainhaler® (THR device) and Flo-Tone® CR (FTCR device), two novel pMDI technique training tools, were evaluated and compared in terms of relative lung and systemic bioavailability and oropharyngeal deposition of salbutamol inhaled from Ventolin® Evohaler® (GlaxoSmithKline) either alone following THR or connected to FTCR. Methods: Sixteen healthy adults inhaled 2 × 100 μg salbutamol puffs (1 minute apart) from Ventolin using the THR device or FTCR device in a two-period, randomized crossover study. A 7-day washout separated THR and FTCR approaches. Immediately after each puff inhalation, each subject gargled with 20 mL water for oropharyngeal deposition determination. Urine samples were collected 0.5 hour (pre-inhalation) and 0.5, 1.0, and 2.0 hours post-inhalation. Urine was then pooled till 24-hour post-inhalation. The relative lung bioavailability (0- to 0.5-hour urinary salbutamol excretion-USAL0.5) and relative systemic bioavailability (0- to 24-hour urinary excretion of salbutamol and its metabolite-USALMET24) were determined. Results: The mean (standard deviation [SD]) USAL0.5 of the THR and FTCR groups was 5.70 (6.43) and 11.39 (9.67) μg, respectively. The mean (SD) oropharyngeal deposition was 11.11 (4.37) and 6.09 (1.89) μg, respectively. The THR and FTCR devices were statistically significantly different in USAL0.5 and oropharyngeal deposition (p < 0.001), whereas there was no statistically significant difference in USALMET24. Conclusion: The THR device and the FTCR device showed positive impact on inhaled pMDI delivery. Indeed, the FTCR device doubled the relative lung bioavailability and minimized the unwanted oropharyngeal deposition of inhaled salbutamol. In practice, these pMDI trainers would complement and maintain VT. Study Registration: The study was registered on the ISRCTN registry (Reference: ISRCTN88332465-06/12/2017 [Prospectively Registered]).

Keywords: oropharyngeal deposition; pMDI technique; relative lung bioavailability; spacer; urinary salbutamol excretion; verbal inhaler training.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Albuterol*
  • Biological Availability
  • Bronchodilator Agents*
  • Cross-Over Studies
  • Humans
  • Lung
  • Metered Dose Inhalers
  • Nebulizers and Vaporizers
  • Water


  • Bronchodilator Agents
  • Water
  • Albuterol