Pharmacokinetics of fluticasone propionate multidose, inhalation-driven, novel, dry powder inhaler versus a prevailing dry powder inhaler and a metered-dose inhaler

Abstract

Background: A novel inhalation-driven multidose dry powder inhaler (MDPI) that eliminates the need for the patient to coordinate device actuation with inhalation has been developed for delivery of inhaled asthma medications. Objective: To characterize the pharmacokinetics of single-dose fluticasone propionate (Fp) MDPI compared with single doses of Fp dry powder inhaler (DPI) and a metered-dose inhaler (MDI) in healthy subjects. Methods: This was a single-center, open-label, randomized, three-period crossover, single-dose pilot study in healthy adults ages 18 to 45 years. Eligible subjects (N = 18) were randomized to one of six treatment sequences that contained three treatment arms: Fp MDPI 400 μg/inhalation × two inhalations (800 μg total dose); Fp DPI 250 μg/inhalation × four (1000 μg total dose); and Fp MDI 220 μg/inhalation × four (880 μg total dose). Pharmacokinetics (area under concentration-versus-time curve [AUC], maximum plasma concentration [C_max], time to C_max [t_max], and elimination half-life [t_½]), safety, and tolerability were assessed for each treatment. Results: Plasma Fp concentration-versus-time curves were comparable across treatments. Geometric mean AUC_0-t and C_max for Fp MDPI 800 μg were 19% and 18% higher, respectively, compared with Fp DPI 1000 μg, and 47% and 82% higher, respectively, compared with Fp MDI 880 μg. Median t_max (60.0‐60.6 minutes) and median t_1/2 (9.1‐9.8 hours) were comparable across the three treatments. Single-dose Fp was well tolerated, with no new safety issues noted. Conclusion: Single-dose administration of Fp MDPI 800 μg produced systemic exposure comparable with those for Fp DPI 1000 μg and Fp MDI 880 μg.