AN ASSESSMENT OF THE SYSTEMIC EFFECTS OF SINGLE AND REPEATED DOSES OFINHALED FLUTICASONE PROPIONATE AND INHALED BUDESONIDE IN HEALTHY-VOLUNTEERS

The systemic effects of single and multiple doses of inhaled fluticaso ne propionate (FP) and budesonide were examined in 24 healthy male vol unteers (age range 18-29 years). The study was of an open, placebo-con trolled, randomized, three-way crossover design. On each study day, mu ltiple blood samples were taken over a 20 h period after drug administ ration (after a single dose and after the last of seven doses) and are a under- the curve (AUC(0-20)) for plasma cortisol and white blood cel l (WBC) counts was calculated. Results: The present study shows that m ultiple dosing with FP 1.0 mg b.i.d. for 3.5 days (seven doses) result ed in a marked cortisol suppression from placebo which, at 55%, was mo re than double that seen with a single dose (25% suppression). Multipl e dosing with budesonide 0.8 mg b.i.d. resulted in a 34% suppression i n plasma cortisol compared with a suppression of 26% with a single dos e. The increase in systemic activity of FP after multiple dosing is co nfirmed 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 followi ng multiple dosing as compared with a single dose. This increase in sy stemic effect from single dosing to multiple dosing is significantly g reater for FP than for budesonide.