The study addressed the question whether the novel inhaled prodrug corticosteroid ciclesonide is equally effective when inhaled in the morning compared to the evening.For this purpose a double-blind, randomized, parallel group study was initiated in which 209 asthmatic patients (forced expiratory volume in one second~50 -90% predicted) inhaled either 200 mg ciclesonide in the morning or in the evening, for 8 weeks. Efficacy was assessed by means of spirometry as well as daily recordings of morning and evening peak expiratory flow (PEF), symptoms and use of rescue medication. The 24-h urinary cortisol excretion was measured to evaluate any effect on hypothalamic-pituitary-adrenol axis.Ciclesonide significantly improved asthma control. Morning and evening administration was shown to be equally effective for the different spirometry variables, evening PEF, symptoms, use of rescue medication and number of asthma exacerbations. Regarding morning PEF, the improvements after evening dosing were more prominent and equivalence of morning and evening administration could not be demonstrated. No relevant influence on cortisol excretion was found.Overall, the study indicates that ciclesonide can be given either in the morning or in the evening to meet the patients9 preference and individual medical needs, although evening administration may lead to a more pronounced improvement in morning peak expiratory flow. Eur Respir J 2001; 17: 1083-1088. The study was supported by Byk Gulden Pharmaceuticals.Inhaled corticosteroids have become the mainstay of therapy for patients with asthma. However, as with other inhaled or oral asthma drugs, compliance to inhaled steroids is often poor [1]. Among the manifold reasons underlying noncompliance, complicated regimens and dosing frequency are considered to be significant factors. Initially, inhaled steroids were recommended to be used four-times a day. Although such a regimen might be more effective than twice-daily dosing [2], in daily life higher compliance with a twicedaily regimen might well compensate reduced efficacy [3]. Meanwhile numerous studies have shown that in the majority of patients a twice-daily schedule can effectively control asthma and this is presently the standard scheme. Additionally, it was suggested that decreasing the dosing frequency to once daily might further enhance adherence to the prescribed regimen [4]. In the past the efficacy of once-daily administration was, therefore, tested with a number of inhaled steroids in patients with mild-to-moderate asthma [5].Ciclesonide is a novel prodrug glucocorticosteroid in development for the treatment of asthma. Ciclesonide which has a chiral centre in the acetal side chain, exists as two epimers with different receptor affinities and metabolization rates. Only R-ciclesonide was selected for clinical development (referred to as ciclesonide from now on). Ciclesonide itself is inactive and needs to be cleaved by esterases to bind to the glucocorticoid receptor. The efficacy of ciclesonide in humans was demonstr...

In 11 patients, in whom a lung lobe or whole lung was to be resected, a single dose of 1.6 mg inhaled budesonide was given pre-operatively. In 9 of them, concentrations of the drug in both lung tissue and blood plasma were measured. Budesonide concentrations in lung tissue, at least 90 min after dosage, were 2.1-8.9 nmol kg-1. Concentrations in blood plasma (0.27-1.1 nmol kg-1) were 1/8th of those in lung tissue.