HPA-axis effects of nebulised fluticasone propionate compared with oral prednisolone in childhood asthma

• Published in: Respiratory medicine 2002-08, Vol.96 (8), p.625-631
• Main Authors: PRICE, J., LENNEY, W., DUNCAN, C., GREEN, L., FLOOD, Y., DALEY-YATES, P., BARNACLE, H., EFTHIMIOU, J.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Administration, Oral; Androstadienes - administration & dosage; Anti-Inflammatory Agents - administration & dosage; asthma; Asthma - drug therapy; Asthma - urine; Biological and medical sciences; Child; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; fluticasone propionate; Humans; Hydrocortisone - urine; Hypothalamo-Hypophyseal System - drug effects; Male; Medical sciences; NebulesTM; Pharmacology. Drug treatments; Pituitary-Adrenal System - drug effects; prednisolone; Prednisolone - administration & dosage; Respiratory system; Treatment Outcome; urinary cortisol
• ISSN: 0954-6111; 1532-3064
• DOI: 10.1053/rmed.2002.1323

The aim of this study was to compare the effect of 7 days nebulised fluticasone propionate (FP) with oral prednisolone on 24-h urinary-free cortisol excretion, systemic exposure and safety. This was a randomised, double-blind, double-dummy, two-way crossover study. Thirty-one children (19 male, 12 female, mean age 8 years) with stable asthma were randomly assigned to 7 days treatment with either FP NebulesTM (2×0.5 mg/2 ml bd) or prednisolone tablets once daily (2 mg/kg/day for 4 days [maximum 40 mg] followed by 1 mg/kg/day or half the original dose for 3 days [maximum 20 mg]). After a 2–4 week washout period, patients received the second treatment for 7 days, followed by a 2-week follow-up visit. The primary outcome measure was 24-h urinary-free cortisol concentrations corrected for creatinine. Nebulised FP (1 mg bd) had significantly less effect on 24-h urinary-free cortisol excretion than oral prednisolone (8.9 ng/ml for FP and 5.0 ng/ml for prednisolone, P=0.001). Systemic exposure to FP was also low. In conclusion, FP NebulesTM had significantly less effect on hypothalamic–pituitary–adrenal axis function than oral prednisolone in asthmatic children when used at doses recommended for the treatment of an acute exacerbation of asthma.