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

Abstract

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 max , AUC 0-t , AUC 0-inf , t max , and t ½ 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 max , AUC 0-t , and AUC 0-inf ) 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 ½ values were similar across treatments. Salmeterol C max was 20% lower and AUC 0-t and AUC 0-inf were approximately 50% lower with FS MDPI versus FS DPI. Median t max and geometric mean t ½ 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.

Pharmacokinetics of Single and Repeat Doses of Fluticasone Furoate/Umeclidinium/Vilanterol in Healthy Chinese Adults

“…38 Similarly, an analysis of fluticasone propionate in adolescents and adults with persistent asthma found that the t max ranged from 0.5 to 4.0 hours at both 200 and 500 µg doses. 39 There was an apparent discrepancy between the reported half-lives for UMEC (0.36 hours) and VI (0.52 hours) and the accumulation observed in this study. However, the overall systemic concentrations for both UMEC and VI were still low, with relatively high LLoQ (10 pg/mL).…”

“…For example, a PK analysis of fluticasone propionate in healthy adults found a t max ranging from 31.2 to 360 minutes at a dose of 880 µg delivered by a metered‐dose inhaler . Similarly, an analysis of fluticasone propionate in adolescents and adults with persistent asthma found that the t max ranged from 0.5 to 4.0 hours at both 200 and 500 µg doses …”