Pharmacokinetics of fluticasone propionate multidose, inhalation-driven, novel, dry powder inhaler versus Diskus and metered-dose inhalers.

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 Diskus (a dry powder inhaler) 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 micrograms/inhalation X two inhalations (800 micrograms total dose); Fp Diskus 250 micrograms/inhalation X four (1000 micrograms total dose); and Fp MDI 220 micrograms/inhalation X four (880 micrograms total dose). Pharmacokinetics (area under concentration-versus- time curve [AUC], maximum plasma concentration [Cmax], time to Cmax [tmax], and elimination half-life [t1⁄2]), 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 micrograms were 19% and 18% higher, respectively, compared with Fp Diskus 1000 micrograms, and 47% and 82% higher, respectively, compared with Fp MDI 880 micrograms. Median tmax (60.0-60.6 minutes) and median t1/2 (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 micrograms produced systemic exposure comparable with those for Fp Diskus 1000 micrograms and Fp MDI 880 micrograms.