AN ASSESSMENT OF THE SYSTEMIC ACTIVITY OF SINGLE DOSES OF INHALED FLUTICASONE PROPIONATE IN HEALTHY-VOLUNTEERS

1 The systemic effects of inhaled fluticasone propionate (FP), administered via Diskhaler(R), 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 mu g FP, 500 mu g FP and 1000 mu g FP, respectively. A single dose of budesonide, 800 mu g (via Turbuhaler(R)), 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 mu g 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.