Similar Results in Children with Asthma for Steady State Pharmacokinetic Parameters of Ciclesonide Inhaled with or without Spacer

Abstract

Background:Ciclesonide is an inhaled corticosteroid administered by a metered dose inhaler (MDI) to treat bronchial asthma. After inhalation, the inactive ciclesonide is converted by esterases in the airways to active metabolite desisobutyryl-ciclesonide (des-CIC).Aim:To compare the pharmacokinetic (PK) parameters of des-CIC in children after administration of therapeutic dose of ciclesonide with and without spacer (AeroChamber Plus™).Methods:Open-label, 3 period, cross over, repeated dose, PK study in 37 children with mild to moderate stable asthma (age: 6–11 y; body weight: 20–53 kg). During each 7-day treatment period, ciclesonide was inhaled once in the morning: A) 160 μg MDI with spacer, B) 80 μg MDI with spacer, and C) 160 μg MDI without spacer. Serum PK parameters of ciclesonide and des-CIC were determined on Day 7 of each period. The primary PK parameters were the AUCτ and Cmax for des-CIC.Results:Inhaling ciclesonide with spacer led to a dose proportional systemic exposure (AUCτ) of des-CIC (0.316 μg*h/L for 80 μg and 0.663 μg*h/L for 160 μg). The dose-normalized systemic exposure for des-CIC (based on AUCτ) was 27% higher after inhalation of ciclesonide 80 μg or 160 μg with spacer than without spacer; the corresponding Cmax values for des-CIC were, respectively, 63% and 55% higher with spacer. No clinically relevant abnormalities or adverse drug reactions were observed.Conclusions:Inhalation of therapeutic ciclesonide dose with spacer led to a slight increase in the systemic exposure of des-CIC, which does not warrant dose adjustment.

Extra‐fine particle inhaled corticosteroids, pharma‐cokinetics and systemic activity in children with asthma

“…. The data were derived from in vitro studies , from studies in healthy males and healthy males and females , from studies in males and females and children with asthma, and from review papers . The studies in adults comprised populations of 6 , 8 , 9 and 12 subjects; the paediatric studies 18 and 34 pre‐pubertal children.…”

“…The data were derived from in vitro studies , from studies in healthy males and healthy males and females , from studies in males and females and children with asthma, and from review papers . The studies in adults comprised populations of 6 , 8 , 9 and 12 subjects; the paediatric studies 18 and 34 pre‐pubertal children. Treatments were single doses of 6.9 mg (oral administration) and 0.64 mg (intravenous administration) ciclesonide , a single dose of ciclesonide 40 μg , 6‐day treatment with 50 and 100 μg beclomethasone dipropionate , a single dose of 1280 μg ciclesonide , a single dose of 200 and 400 μg beclomethasone dipropionate , and 7‐day treatment with ciclesonide 80 and 160 μg/day .…”

“…The studies in adults comprised populations of 6 , 8 , 9 and 12 subjects; the paediatric studies 18 and 34 pre‐pubertal children. Treatments were single doses of 6.9 mg (oral administration) and 0.64 mg (intravenous administration) ciclesonide , a single dose of ciclesonide 40 μg , 6‐day treatment with 50 and 100 μg beclomethasone dipropionate , a single dose of 1280 μg ciclesonide , a single dose of 200 and 400 μg beclomethasone dipropionate , and 7‐day treatment with ciclesonide 80 and 160 μg/day . Pharmacokinetic key data of extra‐fine ciclesonide and beclomethasone dipropionate are given in Table .…”

“…The reported clearance rates of des‐CIC and 17‐BDP (Table ) are high, thus suggesting extra‐hepatic metabolism . Studies assessing once‐daily administration of extra‐fine ciclesonide and beclomethasone dipropionate in doses of 160 and 200 μg, respectively, in 5‐ to 11‐ and 9‐ to 12‐year‐old children with asthma found the active metabolites to be detectable in serum up to 12 and 6 h later. Although the bioavailability of the two molecules is high, the systemic exposure may be less than would be expected due to their clearance as compared to other corticosteroids .…”

From inhaler to lung: clinical implications of the formulations of ciclesonide and other inhaled corticosteroids

“…However, Drollmann et al observed that the pharmacokinetic properties of the active metabolite des-CIC were comparable after inhalation with and without an AeroChamber Plus ® (Trudell Medical International, London, Ontario, Canada) spacer,46 suggesting that CIC-HFA pMDI does not require a spacer for optimal delivery. The results from a pediatric study that enrolled children (aged 6–11 years) indicated that the use of a spacer resulted in a slight increase in the systemic exposure of des-CIC and also showed that inhaled CIC (80 μg and 160 μg) with spacer led to dose proportional systemic exposure 47. There is some evidence which suggests the use of a spacer device enhances pMDI therapy by reducing the amount of drug deposited in the oropharyngeal region, leading to fewer instances of local and systemic side effects.…”