Lung deposition and systemic bioavailability of dose delivered to smoker compared with non-smoker COPD subjects

Inhaled drugs are the most commonly used class of medications for COPD subjects. No studies have been performed to assess the influence of smoking on lung deposition of aerosolized medication, especially for the exacerbated COPD subject. The present study aimed to assess the influence of smoking on the lung deposition of the aerosol delivered to exacerbated COPD subjects.

Twenty-four exacerbated COPD subjects using automatic continuous positive airway pressure (Auto-CPAP), 12 smokers (six females) and 12 non-smokers (six females) were recruited in the study. The subjects participated in the study received four salbutamol study doses; 1200 µg (12 puffs 100 µg/puff) of salbutamol emitted from pMDI canister connected to AeroChamber MV spacer; 1200 µg of salbutamol emitted from pMDI canister connected to Combihaler spacer; 1 mL of salbutamol respirable solution (5000 µg/mL) nebulized by Aerogen Solo connected to its T-piece; and 1 mL of salbutamol respirable solution nebulized by Aerogen Solo connected to Combihaler spacer with 2 puffs salbutamol MDI (200 µg salbutamol) before nebulisation. The subjects were randomised to receive the four selected dose-adaptor combination in a sealed envelope design on days 1, 3, 5 and 7. A washout period of 24 hours was provided between each salbutamol dosing. Auto-CPAP was adjusted at non-invasive ventilation mode with the integrated heated humidifier, as a source of humidity. Urine samples were provided by subjects, 30 minutes and cumulatively 24 hours post inhalation, as an index of the relative and systemic bioavailability, respectively, and aliquots were retained for salbutamol analysis using solid-phase extraction and high-performance liquid chromatography (HPLC). On day 2 of the study, a collecting filter was placed between the aerosol generator and the subject's mask so that the subjects would not inhale the salbutamol delivered. The same study doses and/or adapters were delivered to each subject, with filters changed with each dose-adapter combination. Salbutamol entrained on the filter was desorbed to be analysed by the HPLC.

Significantly higher lung deposition (30 minutes urinary salbutamol) was detected with the non-smoker compared with smokers (P < .05). Significantly higher systemic bioavailability (pooled 24-hour urinary salbutamol) for smokers compared with non-smokers was found with Aerogen Solo connected to its T-piece and CombiHaler spacer with pMDI (P < .05) only. Significantly higher amount desorbed from the ex-vivo filter were found from pMDI with both spacers in non-smokers (P < .05) compared with the smokers.

The study demonstrated that smoking reduced the lung deposition of inhaled salbutamol delivered by nebulizer or pMDI. However, the smoking effect on cytochrome p450 was observed to increase systemic absorption of the ingested portion of the inhaled dose. The lower lung deposition and possible higher systemic absorption should be taken into consideration while prescribing inhaled medication to COPD smokers especially exacerbated patients that need ventilation. Further studies are needed.