Using PreciseInhale® for Controlled Volunteer Exposures with Aerosols Extracted from Clinical Inhalers
Per Gerde1,2, Carl-Olof Sjöberg1 Helen Bäckroos1 & Helena Litorp3,4
1Inhalation Sciences AB, Hälsovägen 7, Novum, 141 57 Huddinge, Sweden
2IMM, Karolinska Institutet, Nobels väg 13, 171 77 Stockholm, Sweden
3CTC Clinical Trial Consultants, Dag Hammarskjölds väg 10B, 752 37 Uppsala, Sweden
4 Department of Global Public Health, Karolinska Institutet, 171 77 Stockholm, Sweden
Summary
The PreciseInhale® (PI) platform was used to extract clinical inhaler doses from the pressurized metered dose inhaler (pMDI) Evohaler Seretide forte, Fluticasone Propionate (FP) 250 µg, Salmeterol Xinafoate (SMX) 25 µg and then expose human volunteers by visually prompting controlled administration from the clinical exposure module of PI. Through 4 study arms the following two comparisons were made: I) The direct inhalation of one dose from the clinical inhaler, according to the label instructions, was compared to the same dose aspirated into the PI and inhaled by the volunteers, following prompted instructions. II) Six subdivided fractions of one dose from the Evohaler was inhaled and targeted to the peripheral lung and the central airways respectively, using the bolus breath hold method provided by the PI. Results show that, compared to direct inhalation from the inhaler, instead extracting the clinical inhaler dose into the PI and then controlling the exposure from the PI both increase the lung deposited dose of drug and the dosing precision. The peripheral lung bolus of FP had a 98% deposition upon inhalation compared to 58% deposition of the central airway bolus. FP had similar pharmacokinetics in both regions, whereas SMX had a significantly higher Cmax following exposure of the peripheral lung.
Key Message
By administering clinical inhalers via PreciseInhale® an improved precision during whole lung exposures was achieved and inhaler aerosol boli could be targeted to different lung regions, which may improve in silico models describing the link between the elusive site-of-entry dosimetry in lungs and the measurable pharmacokinetics of the systemic circulation.