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. METHODS: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 microg per day and 750 microg per day) and BUD (400 microg per day and 800 microg 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 microg) 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 nmol.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; PL 5.9 nmol.mmol(-1). CONCLUSION: Repeated doses of FP 750 microg once daily caused greater adrenal suppression than BUD 800 microg 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 microg once daily nor BUD 400 microg once daily produced detectable adrenal suppression.
RCT Entities:
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. METHODS: 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 microg per day and 750 microg per day) and BUD (400 microg per day and 800 microg 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 microg) 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 nmol.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; PL 5.9 nmol.mmol(-1). CONCLUSION: Repeated doses of FP 750 microg once daily caused greater adrenal suppression than BUD 800 microg 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 microg once daily nor BUD 400 microg once daily produced detectable adrenal suppression.