title: Extra-fine particle inhaled corticosteroids, pharma-cokinetics and systemic activity in children with asthma.
abstract: During recent years, extra-fine particle inhaled corticosteroids with a median aerodynamic diameter ≤2 μm have been introduced in the treatment of asthma. The aim of this paper was to review pharmacokinetics and systemic activity of extra-fine particle hydroalkane pressurized metered dose inhaled (pMDI) ciclesonide and beclomethasone dipropionate in children. A literature review was performed. Systemic bioavailability of oral and pulmonary deposition of extra-fine ciclesonide and beclomethasone dipropionate was 52% and 82%, the half-life in serum 3.2 and 1.5 h and first-pass hepatic metabolism >99% and 60%, respectively. Secondary analyses of urine cortisol/creatinine excretion found no effects of ciclesonide pMDI between 40 and 320 μg/day or of beclomethasone dipropionate pMDI between 80 and 400 μg/day. Ciclesonide pMDI 40, 80 and 160 μg/day caused no effects on short-term lower leg growth rate as assessed by knemometry. Ciclesonide 320 μg/day was associated with a numerically short-term growth suppression equivalent to 30% which was similar to 25% and 36% suppression caused by beclomethasone dipropionate HFA and CFC 200 μg/day, respectively. Consistent with the differences in key pharmacokinetic features, beclomethasone dipropionate is associated with a systemic activity detected by knemometry at a lower dose than ciclesonide. Whether that correlates with a clinically important difference remains to be explored. Assessments of systemic activity of beclomethasone dipropionate <200 μg/day and of ciclesonide >180 μg/day as well as head-to-head comparisons are warranted. Preferably, such studies should apply the sensitive method of knemometry.
authors.affiliation: Asthma and Allergy Clinic, Children's Clinic Randers, Randers, Denmark.
authors.forename: Ole D
authors.initials: OD
authors.lastname: Wolthers
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000336:Aerosols; D000367:Age Factors; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D001682:Biological Availability; D001711:Biotransformation; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D006207:Half-Life; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D036501:Metered Dose Inhalers; D010316:Particle Size; D065589:Respiratory Tract Absorption; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000336:Aerosols; D018927:Anti-Asthmatic Agents; D004338:Drug Combinations
keywords: asthma; beclomethasone dipropionate; bioavailability; ciclesonide; cortisol; fine particle; inhaled corticosteroids; knemometry; pharmacokinetics; systemic activity