Objective: The aim of these studies was to compare the pharmacokinetics of inhaled fluticasone propionate (FP) after repeated administration via the Diskus(R) or Diskhaler(R) dry powder inhalers (DPIs) to patients with mild-to-moderate asthma. Methods: Both studies evaluated the pharmacokinetics of inhaled administration of FP via a DPI to patients with mild-to-moderate asthma, according to a randomised, double-blind, placebo-controlled design. In the first study, FP 100 mug or 500 mug was administered twice daily via the Diskhaler(R) for 6 weeks and, in the second, FP 500 mug was administered via the Diskus(R) or Diskhaler(R) for 12 weeks. Results: In the first study, plasma FP concentrations could be detected consistently only with the higher dose; the lower dose produced concentrations close to or below the 0.025 mug/L quantification limit of the radioimmunoassay used. From detailed analysis of a subgroup of patients receiving the 500 mug dosage, steady-state plasma FP concentrations were attained within one week of commencing treatment. After 4 weeks, the maximum plasma FP concentration (C-max) in this subgroup was 0.096 mug/L [95% confidence interval (CI) 0.066-0.141] and the area under the plasma FP concentration-time curve up to the last quantifiable concentration (AUC(last)) was 0.491 mug/L . h (95% CI: 0.256-0.940). The steady-state to single dose accumulation ratio for FP after twice-daily administration varied between patients: a ratio of approximately 1.7 was recorded after comparison of C-max at week 4 and day 1. In the second study, the point estimate of the Diskus(R) to Diskhaler(R) ratio for C-max in all patients was 0.91 (90% CI: 0.76-1.10) after 4 weeks' treatment. From a detailed analysis of a subgroup of patients, the corresponding ratio for AUC(last) at the same time point was 1.15 (90% CI: 0.69-1.94), indicating no significant difference in systemic exposure to FP between the 2 devices. Steady-state kinetics were achieved by week 1: the point estimate ratios of C-max and AUC(last) at week 4 compared with week 1 were 0.88 (90% CI: 0.66-1.16) and 0.95 (90% CI: 0.66-1.36), respectively. Administration of FP via either DPI had no effect on plasma cortisol levels over the 12-hour postdose period. Conclusion: In patients with asthma receiving repeated inhaled doses of FP, the systemic exposure (AUC) after inhalation from the Diskus(R) was similar to that from the Diskhaler(R), with no difference between the DPIs in the effects on cortisol suppression. The 2 DPIs therefore have very similar pharmacokinetic profiles.
