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

Abstract

The pharmacokinetics (PK) and safety of single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) after single and repeat dosing in healthy Chinese adults were assessed. In this open-label study (NCT02837380), subjects received once-daily FF/UMEC/VI 100/62.5/25µg on day 1 and repeat doses on days 2-7. PK parameters (days 1 and 7) included maximum observed concentration (Cmax ) and area under the plasma concentration-time curve (AUC) from time zero (predose) to last time of quantifiable concentration (AUC0-t ). Terminal phase half-life (t½ ) on day 1 was estimated. The primary objective was to assess systemic exposure of FF 100µg, UMEC 62.5µg, and VI 25µg following single-inhaler triple therapy on days 1 and 7. On day 1, geometric mean t½ of UMEC and VI was 0.36 and 0.52hours, respectively; t½ of FF was not representative because of nonquantifiable concentration data. On days 1 and 7, geometric mean Cmax of FF was 10.46 and 27.32 pg/mL, respectively; Cmax of UMEC was 144.14 and 241.35 pg/mL, respectively; and Cmax of VI was 120.42 and 196.78 pg/mL, respectively. AUC0-t of FF was 1.77 and 276.96 pg·h/mL, respectively; AUC0-t of UMEC was 28.44 and 117.19 pg·h/mL, respectively; and AUC0-t of VI, 42.46 and 101.12 pg·h/mL, respectively. The PK of FF/UMEC/VI was as expected for the individual-component PK previously reported in healthy Chinese adults. No new safety signals were observed.