An assessment of the systemic effects of single and repeated doses of inhaled fluticasone propionate and inhaled budesonide in healthy volunteers

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.     

A comparison of the systemic bioactivity of inhaled budesonide and fluticasone propionate in normal subjects.

1. The aim of this study was to compare the systemic bioactivity of low and high doses of inhaled budesonide and fluticasone propionate given by respective dry powder inhaler devices. 2. A randomised, single blind cross-over design was used in nine healthy subjects who were given 800 micrograms day-1 of budesonide Turbohaler (B800) for 1 week, followed by 1 week of 1600 micrograms day-1 (B1600), or fluticasone Diskhaler 750 micrograms day-1 (F750) for 1 week followed by 1 week of 1500 micrograms day-1 (F1500). There was a 1 week washout between treatments with fluticasone or budesonide. A twice daily dosing regime was used and mouth-rinsing was employed to reduce gut bioavailability as well as to obviate local adverse effects. 3. Parameters of hypothalmic-pituitary adrenal (HPA) axis activity and bone metabolism were measured at baseline (B0/F0), at the end of each week of treatment and after the 1 week washout (F0 or B0). 4. Both fluticasone and budesonide significantly (P < 0.05) attenuated the post tetracosactrin serum cortisol at low and high doses whilst early morning cortisol was unchanged. No dose-response effect was observed with either drug, and there was no significant difference between treatment with fluticasone or budesonide. 5. Neither budesonide nor fluticasone produced significant suppression of plasma osteocalcin, although the higher doses of both drugs significantly reduced fasting urinary calcium levels.(ABSTRACT TRUNCATED AT 250 WORDS)