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 mu g day(-1) of budesonide Turbohaler (B-800) for 1 week, followed by 1 week of 1600 mu g day(-1) (B-1600), or fluticasone Diskhaler 750 mu g day(-1) (F-750) for 1 week followed by 1 week of 1500 mu g day(-1) (F-1500). 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 (B-0/F-0), at the end of each week of treatment and after the I week washout (F-0 or B-0). 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. 6 Thus, whilst fluticasone and budesonide exhibited equivalent systemic bioactivity, when appropriate corrections are made for differences in lung deposition between the Turbohaler and Diskhaler, the systemic glucocorticoid activity of fluticasone may be greater than that of budesonide on a microgram equivalent basis. 7 The finding of significant HPA-axis suppression with low doses of fluticasone and budesonide despite the use of mouth rinsing would suggest that absorption across the lung-vascular bed is the major determinant of systemic adverse effects.