1. The systemic effects of inhaled fluticasone propionate (FP), administered via Diskhaler, on the hypothalamo‐pituitary‐adrenal (HPA) axis were assessed primarily by measuring plasma cortisol at frequent intervals for 20 h after drug administration. 2. FP showed a dose‐ related suppression of plasma cortisol measured as area under the plasma cortisol vs time curve (AUC 0‐20). The cortisol suppression (expressed as % fall from placebo) was 8, 19, and 28% for single doses of 250 micrograms FP, 500 micrograms FP and 1000 micrograms FP, respectively. A single dose of budesonide, 800 micrograms (via Turbuhaler), resulted in a 16% cortisol suppression. The cortisol suppression for all three single doses of FP, and for the single dose of budesonide, was statistically significantly different from placebo. 3. Repeated dosing of FP (1000 micrograms twice daily for 3.5 days) resulted in a more marked plasma cortisol suppression; a fall of 65% from placebo (AUC FP 1000 mg twice daily vs AUC placebo, P < 0.001). 4. In a well‐controlled study in healthy volunteers, inhaled FP, in therapeutic doses, was shown to exhibit systemic effects which appear to be more pronounced after repeated dosing.

The results of the present study show that FP-DH suppresses plasma cortisol more than BUD-TBH on a equivalent basis with regard to both magnitude and duration.

The systemic effects of single and multiple doses of inhaled fluticasone propionate (FP) and budesonide were examined in 24 healthy male volunteers (age range 18-29 years). The study was of an open, placebo-controlled, randomized, three-way crossover design. On each study day, multiple blood samples were taken over a 20 h period after drug administration (after a single dose and after the last of seven doses) and area under the curve (AUC(0-20)) for plasma cortisol and white blood cell (WBC) counts was calculated. RESULTS. The present study shows that multiple dosing with FP 1.0 mg b.i.d. for 3.5 days (seven doses) resulted in a marked cortisol suppression from placebo which, at 55%, was more than double that seen with a single dose (25% suppression). Multiple dosing with budesonide 0.8 mg b.i.d. resulted in a 34% suppression in plasma cortisol compared with a suppression of 26% with a single dose. The increase in systemic activity of FP after multiple dosing is confirmed by both the number of subjects with 0800 hours plasma cortisol values below normal limits and by the changes in WBC and differential counts. CONCLUSION. The results of the present study confirm previous findings with regard to the more marked systemic effect of FP following multiple dosing as compared with a single dose. This increase in systemic effect from single dosing to multiple dosing is significantly greater for FP than for budesonide.