Lung Deposition of Tanimilast, an Inhaled Phosphodiesterase-4 Inhibitor, in Patients with Asthma or COPD, Evaluated Using Functional Respiratory Imaging

Background: Tanimilast is a novel phosphodiesterase-4 inhibitor under clinical development for the maintenance therapy of asthma and chronic obstructive pulmonary disease (COPD). Since tanimilast is inhaled, it is important to evaluate lung deposition as part of its clinical development. The current study, therefore, used functional respiratory imaging, a validated, noninvasive quantification imaging methodology, to evaluate the lung deposition of tanimilast in patients with asthma or COPD. Methods: This retrospective study used data from 12 patients with asthma and 12 patients with COPD, primarily selected based on disease severity. Patients with COPD had chronic bronchitis, with minimal high-resolution computerized tomography evidence of emphysema. Total intrathoracic, central, distal, peripheral, and extrathoracic deposition of tanimilast 400 µg and 800 µg was evaluated using three inhalation profiles—inhalation durations of 1, 2, and 3 seconds, with associated peak flows of 100, 60, and 45 L/min, respectively. Results: Intrathoracic deposition as a percentage of the delivered dose was similar in asthma and COPD, with mean ± SD varying between 34.6 ± 8.5% and 44.9 ± 5.9%, increasing slightly with increasing inhalation duration (i.e., from 1 to 3 seconds), whereas extrathoracic deposition decreased progressively. Central deposition was low (<5%) regardless of inhalation duration (2.7 ± 0.9% to 4.4 ± 1.6%). Distal deposition was similar with the two tanimilast doses and although not impacted by inhalation duration was slightly higher in COPD than asthma. Peripheral deposition increased with increasing inhalation duration (e.g., in asthma for tanimilast 400 µg, from 14.1 ± 3.6% for a duration of 1 second to 19.9 ± 4.0% for a duration of 3 seconds) and was higher in asthma than in COPD. Conclusions: Tanimilast effectively reached all levels of the airway in patients with asthma or COPD. Peripheral deposition was enhanced by lower inspiratory flows (i.e., longer inhalation durations), suggesting that specific inhalation strategies may have the potential to improve therapeutic outcomes in obstructive lung diseases.