Effects of inhaled ciclesonide and fluticasone propionate on cortisol secretion and airway responsiveness to adenosine 5 ' monophosphate in asthmatic patients

The efficacy and systemic effects of ciclesonide, a novel glucocorticosteroid, inhaled via pressurized metered-dose inhaler (pMDI) were compared with fluticasone propionate pMDI in 26 patients with asthma, using a randomized, double blind, placebo-controlled, double dummy, 6-period crossover study design. Treatments were placebo, ciclesonide 320 mu g (ex-actuator dose) once daily (o.d.), ciclesonide 640 pg o.d., ciclesonide 640 mu g twice daily (b.i.d.), fluticasone propionate 440 mu g (ex-actuator dose) b.i.d., and fluticasone propionate 880 mu g b.i.d. The primary variable was area under the plasma cortisol concentration-time curve over 24 It (plasma cortisol AUC(0.24), relative to placebo) derived from samples taken every 2 h, on the 9th day of treatment. Secondary variables were 24-h urinary cortisol excretion and PC20 for adenosine 5'-monophosphate (AMP) (relative to placebo and expressed in doubling concentrations). Ciclesonide did not affect 24-h cortisol secretion. Fluticasone propionate suppressed cortisol secretion as demonstrated by a decrease in plasma cortisol AUCO-24, relative to placebo, by 29 % (95 % Cl 15-41) and 59 % (95 % CI 51-66) with 440 and 880 mu g b.i.d., respectively. PC20 more than doubled with each active treatment, but no statistically significant dose-response effect could be established. It was concluded that moderate to high doses of fluticasone propionate suppressed cortisol secretion, that ciclesonide did not suppress cortisol secretion, and that all active treatments decreased hyperresponsiveness to AMP. (c) 2005 Elsevier Ltd. All rights reserved.