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

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 mu g/inhalation x two inhalations (800 mu g total dose); Fp DPI 250 mu g/inhalation x four.(1000,mu g total dose); and Fp MDI 220 mu g/inhalation x four (880 mu g 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(1/2)]), 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 Cmax for Fp MDPI 800 mu g were 19% and 18% higher, respectively, compared with Fp DPI 1000 mu g, and 47% and 82% higher, respectively, compared with Fp MDI 880 mu g. 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 mu g produced systemic exposure comparable with those for Fp DPI 1000 mu g and Fp MDI 880 mu g.