Adrenocortical activity with repeated administration of one-daily inhaled fluticasone propionate and budesonide in asthmatic adults

Objective: The aim of this study was to evaluate the steady-state effects of once-daily inhaled fluticasone propionate (FP) and budesonide (BUD) on adrenocortical activity in asthmatic patients. thods: Ten asthmatic patients with a mean age of 31.2 years, a mean forced expiratory volume in 1 s (FEV1) of 91% predicted and a forced mid-expiratory flow (FEF25-75) of 62.3% predicted were studied in a single-blind randomised crossover design comparing placebo (PL), FP (375 mu g per day and 750 mu g per day) and BUD (400 mu g per day and 800 mu g per day) all given once daily for 4 days at each dose via a pressurised metered dose inhaler (pMDI) at 0800 hours. After 4 days of treatment, plasma cortisol was measured at 0800 hours (24 h after the last dose) and a 10-h overnight urine collection was taken, 14 h after the last dose (2200-0800 hours) for analysis of cortisol and creatinine excretion. Results: Plasma cortisol levels (nmol.l(-1) as geometric mean) at 0800 hours demonstrated a significant difference between the highest doses of FP and BUD (424.1 vs 510.3 nmol.l(-1) respectively) but not between the low doses (506.8 vs 514.9 nmol.l(-1) PL 532.2 nmol.l(-1)). For the highest dose FP (750 mu g) this equated to 20% suppression of 0800 hours plasma cortisol. Likewise, for overnight urinary cortisol output (nmol.10 h(-1), as geometric mean), there was a significant difference at the high doses of FP and BUD (25.5 vs 38.2 nmol 10 h(-1)), but not at the low doses 31.3 vs 34.8 nmole 10 h(-1) PL 32.0 nmol.10 h(-1). For the overnight urinary cortisol/creatinine ratio (nmol.mmol(-1), as geometric mean) there was a similar trend; 4.5 vs 6.1 nmol.mmol(-1) for high dose and 5.6 vs 6.3 nmol.mmol(-1) for low dose; PL5.9 nmol mmol(-1). Conclusion: Repeated doses of FP 750 mu g once daily caused greater adrenal suppression than BUD 800 mu g once daily, when comparing effects on plasma cortisol levels at 0800 hours, 24 h after the last dose, as well as effects on overnight urinary cortisol output. Neither FP 375 mu g once daily nor BUD 400 mu g once daily produced detectable adrenal suppression.