Pharmacokinetics of fluticasone propionate inhaled via the Diskhaler and Diskus powder devices in patients with mild-to-moderate asthma.
OBJECTIVE
The aim of these studies was to compare the pharmacokinetics of inhaled fluticasone propionate (FP) after repeated administration via the Diskus or Diskhaler 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 microg or 500 microg was administered twice daily via the Diskhaler for 6 weeks and, in the second, FP 500 microg was administered via the Diskus or Diskhaler 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 microg/L quantification limit of the radioimmunoassay used. From detailed analysis of a subgroup of patients receiving the 500 microg dosage, steady-state plasma FP concentrations were attained within one week of commencing treatment. After 4 weeks, the maximum plasma FP concentration (Cmax) in this subgroup was 0.096 microg/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 (AUClast) was 0.491 microg/L x 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 Cmax at week 4 and day 1. In the second study, the point estimate of the Diskus to Diskhaler ratio for Cmax 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 AUClast 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 Cmax and AUClast 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.


CONCLUSIONS
In patients with asthma receiving repeated inhaled doses of FP, the systemic exposure (AUC) after inhalation from the Diskus was similar to that from the Diskhaler, with no difference between the DPIs in the effects on cortisol suppression. The 2 DPIs therefore have very similar pharmacokinetic profiles.
Falcoz
C
C
Clinical Pharmacology, Glaxo Wellcome Research and Development, Greenford, Middlesex, England. cf18544@GlaxoWellcome.co.uk
Horton
J
J
Mackie
A E
AE
Harding
S M
SM
Daley-Yates
P T
PT
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000730:Androstadienes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001249:Asthma / Q000097:blood / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D000068298:Fluticasone; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011208:Powders
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D011208:Powders; D000068298:Fluticasone