Pharmacokinetics of fluticasone propionate inhaled via the Diskhaler® and Diskus® powder devices in healthy volunteers

Objective: The aim of these studies was to determine the absolute bioavailability in healthy volunteers of inhaled fluticasone propionate (FP) administered as a single dose via the Diskhaler(R) and Diskus(R) powder devices, and the pharmacokinetics of inhaled FP after repeated administration via the Diskhaler(R) device. Methods: In 2 of the studies, single inhaled doses of FP were administered via the Diskhaler(R) and the Diskus(R) powder devices, and, in the third study, repeated doses of FP were administered via the Diskhaler(R). In the single dose studies, 12 healthy volunteers were randomised to receive FP 1000 mug by inhalation and FP 250 mug intravenously, using a double-blind crossover design. In the repeated dose study, 24 healthy volunteers received FP 1000 mug twice daily for 7.5 days. Results: Systemic exposure to FP after administration of a single 1000 mug inhaled dose of FP via the 2 powder devices was similar; the area under the plasma FP concentration-time curve (AUC) to infinite time (AUC,) was 2.08 mug/L . h [95% confidence intervals (CI): 1.63-2.64] for Diskhaler(R) and 2.49 mug/L . h (95% CI: 2.09-2.96) for Diskus(R). Maximum plasma FP concentration (C-max was 0.34 mug/L for both devices. Mean bioavailability values via the Diskhaler(R) and Diskus(R) were 11.9% (95% CI: 9.0-15.7%) and 16.6% (95% CI: 13.6-20.3%), respectively. No clinically significant reductions in urinary cortisol excretion were recorded in these 2 studies. After repeated administration with the Diskhaler(R), steady state was achieved by dose 3 (i.e. day 2) onwards. After dose 15, the AUC up to 12 hours (AUC(12h)) was 2.25 mug/L . h and Cmax was 0.38 mug/L. The mean steady-state to single dose accumulation ratio after twice-daily administration was 1.49 (95% CI: 1.36-1.62). Conclusion: The pharmacokinetics of FP administered by the 2 powder devices are similar in healthy volunteers, although systemic bioavailability was greater with the Diskus(R).