The pharmacokinetics, safety, and tolerability of single, high-strength doses of fluticasone propionate and fluticasone propionate/salmeterol delivered via a novel multidose dry powder inhaler in adolescents and adults with persistent asthma.

OBJECTIVE

Characterize fluticasone propionate (Fp) and combination fluticasone propionate and salmeterol (FS) pharmacokinetic and safety profiles, delivered via a novel, inhalation-driven, multidose dry powder inhaler (MDPI).

METHODS

This multicenter, open-label, four-period crossover, single-dose study randomized patients aged ≥12 years with persistent asthma to Fp MDPI 200 mcg, FS MDPI 200/12.5 mcg, Fp dry powder inhaler (DPI) 500 mcg (250 mcg × 2 inhalations), or FS DPI 500/50 mcg. Blood samples for determination of Fp and salmeterol pharmacokinetic parameters including C, AUC, AUC, t, and t were collected predose through 36 h postdose (14 time points). Safety assessments comprised adverse events, vital signs, and physical examinations. The institutional review board approved the study protocol.

RESULTS

The pharmacokinetic analysis set and safety population each included 40 patients. Fp systemic exposure (C, AUC, and AUC) was highest for Fp DPI 500 mcg and similar for Fp MDPI 200 mcg, FS MDPI 200/12.5 mcg, and FS DPI 500/50 mcg. Fp geometric mean t values were similar across treatments. Salmeterol C was 20% lower and AUC and AUC were approximately 50% lower with FS MDPI versus FS DPI. Median t and geometric mean t were similar between FS MDPI and FS DPI. Adverse events were similar across treatments with no relevant changes in vital signs, physical examinations, or hematology test results.

CONCLUSIONS

Fp MDPI and FS MDPI produced similar or lower systemic exposure to Fp and salmeterol, despite lower doses, versus conventional DPI devices, suggesting improved efficiency due to formulation and device differences.