Dose-response for adrenal suppression with hydrofluoroalkane formulations of fluticasone propionate and beclomethasone dipropionate

Aims With the recent introduction of hydrofluoroalkane (HFA) inhalers it is important to know the relative systemic safety profiles of inhaled cortico steroids. We therefore decided to compare systemic bioavailability of HFA-b eclomethasone dipropionate (BDP) vs HFA-fluticasone propionate (FP). Methods Sixteen healthy volunteers were randomised in placebo-controlled si ngle blind cross-over fashion to receive 3 weeks with HFA-FP or HFA-BDP, gi ven as 1 week cumulative doubling doses (nominal ex-valve) of 500, 1000 and 2000 mug day(-1), with a 1 week placebo run-in and wash-out. Overnight (22 .00 h to 08.00 h) and early morning (08.00 h) urinary cortisol/creatinine e xcretion and 08.00 h serum cortisol were measured after each placebo and do sing period. All data were log-transformed to normalize their distribution. Results Urine and serum cortisol were suppressed by 2000 mug FP and BDP vs placebo and by 1000 mug BDP vs placebo for urinary cortisol/creatinine (P < 0.05). Overnight urinary cortisol/creatinine ratio (the primary endpoint) was suppressed more by 1000 mug BDP vs 1000 mug FP (P < 0.05), amounting to a geometric mean fold difference (95% CI) of 1.64 (1.04-2.56). There were also more individual low values less than 3 nmol mmol(-1) with BDP than FP at 1000 mug: n = 8/16 vs n = 2/16 (P < 0.05). Conclusions There was dose-related suppression of corrected urinary cortiso l/creatinine with the HFA formulations of BDP and FP. Suppression of overni ght urinary cortisol/creatinine ratio was significantly greater with HFA-BD P than HFA-FP at 1000 mug. This suggests that the greater glucocorticoid po tency of HFA-FP may be offset by the greater lung bioavailability of HFA-BD P.