Skip to main content
NCBI home page
Thorax logoLink to Thorax
. 1997 Aug;52(8):686–689. doi: 10.1136/thx.52.8.686

Adrenocortical activity with repeated twice daily dosing of fluticasone propionate and budesonide given via a large volume spacer to asthmatic school children

B J Lipworth, D J Clark, L C McFarlane
PMCID: PMC1758624  PMID: 9337826

Abstract

BACKGROUND: In a previous single dosing study in asthmatic school children fluticasone propionate produced significantly greater suppression of overnight urinary cortisol excretion than budesonide at high doses of 800 micrograms/day or greater. The aim of this study was to assess whether conventional lower doses of both drugs cause adrenal suppression when given at steady state twice daily by large volume spacer on a microgram equivalent basis in asthmatic school children. METHODS: Eight school children of mean age 12.1 years with stable asthma of mild to moderate severity (forced expiratory volume in one second (FEV1) 78.6% predicted, mid forced expiratory flow rate (FEF25- 75) 72.5% predicted), on 400 micrograms/day or less of inhaled corticosteroid, were studied in a single blind (investigator blind), placebo controlled, crossover design comparing inhaled budesonide and fluticasone propionate 100 micrograms bid and 200 micrograms bid. Each dose was given at 08.00 hours and 20.00 hours for four days by metered dose inhaler via their respective large volume spacers with mouth rinsing. Measurements were made of overnight urinary cortisol and creatinine excretion after the eighth dose. RESULTS: Neither drug produced significant suppression of overnight urinary cortisol or cortisol/creatinine excretion compared with pooled placebo and there were no differences between the drugs. Only one subject with each drug at 200 micrograms twice daily had abnormally low urinary cortisol excretion of < 10 nmol/12 hours. Ratios for the fold difference between active treatment versus placebo for urinary cortisol excretion were (as means and 95% confidence intervals for difference): budesonide 100 micrograms b.i.d 1.03 (95% CI 0.46 to 1.61), budesonide 200 micrograms b.i.d 1.04 (95% CI 0.62 to 1.46); fluticasone 100 micrograms b.i.d 1.11 (0.45 to 1.77), fluticasone 200 micrograms b.i.d 1.12 (0.78 to 1.47). Likewise, there were no significant differences in overnight urinary cortisol/creatinine excretion. CONCLUSIONS: With repeated twice daily administration at steady state across a dose range of 200-400 micrograms/day no evidence of significant adrenal suppression was found using the sensitive marker of overnight urinary cortisol excretion for either fluticasone propionate or budesonide given via a large volume spacer. These results emphasise the good safety profile in children of these inhaled steroids at conventional dose levels, which have proven antiasthmatic efficacy. 




Full Text

The Full Text of this article is available as a PDF (133.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barnes P. J. Inhaled glucocorticoids for asthma. N Engl J Med. 1995 Mar 30;332(13):868–875. doi: 10.1056/NEJM199503303321307. [DOI] [PubMed] [Google Scholar]
  2. Berg E. In vitro properties of pressurized metered dose inhalers with and without spacer devices. J Aerosol Med. 1995 Sep;8 (Suppl 3):S3–S11. doi: 10.1089/jam.1995.8.suppl_3.s-3. [DOI] [PubMed] [Google Scholar]
  3. Boorsma M., Andersson N., Larsson P., Ullman A. Assessment of the relative systemic potency of inhaled fluticasone and budesonide. Eur Respir J. 1996 Jul;9(7):1427–1432. doi: 10.1183/09031936.96.09071427. [DOI] [PubMed] [Google Scholar]
  4. Clark D. J., Clark R. A., Lipworth B. J. Adrenal suppression with inhaled budesonide and fluticasone propionate given by large volume spacer to asthmatic children. Thorax. 1996 Sep;51(9):941–943. doi: 10.1136/thx.51.9.941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clark D. J., Grove A., Cargill R. I., Lipworth B. J. Comparative adrenal suppression with inhaled budesonide and fluticasone propionate in adult asthmatic patients. Thorax. 1996 Mar;51(3):262–266. doi: 10.1136/thx.51.3.262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gustafsson P., Tsanakas J., Gold M., Primhak R., Radford M., Gillies E. Comparison of the efficacy and safety of inhaled fluticasone propionate 200 micrograms/day with inhaled beclomethasone dipropionate 400 micrograms/day in mild and moderate asthma. Arch Dis Child. 1993 Aug;69(2):206–211. doi: 10.1136/adc.69.2.206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Högger P., Rohdewald P. Binding kinetics of fluticasone propionate to the human glucocorticoid receptor. Steroids. 1994 Oct;59(10):597–602. doi: 10.1016/0039-128x(94)90054-x. [DOI] [PubMed] [Google Scholar]
  8. Lipworth B. J. Airway and systemic effects of inhaled corticosteroids in asthma: dose response relationship. Pulm Pharmacol. 1996 Feb;9(1):19–27. doi: 10.1006/pulp.1996.0002. [DOI] [PubMed] [Google Scholar]
  9. Lönnebo A., Grahnén A., Jansson B., Brundin R. M., Ling-Andersson A., Eckernäs S. A. An assessment of the systemic effects of single and repeated doses of inhaled fluticasone propionate and inhaled budesonide in healthy volunteers. Eur J Clin Pharmacol. 1996;49(6):459–463. doi: 10.1007/BF00195931. [DOI] [PubMed] [Google Scholar]
  10. Olsson B. Aerosol particle generation from dry powder inhalers: can they equal pressurized metered dose inhalers? J Aerosol Med. 1995 Sep;8 (Suppl 3):S13–S19. doi: 10.1089/jam.1995.8.suppl_3.s-13. [DOI] [PubMed] [Google Scholar]
  11. Pedersen S., Steffensen G., Ekman I., Tönnesson M., Borgå O. Pharmacokinetics of budesonide in children with asthma. Eur J Clin Pharmacol. 1987;31(5):579–582. doi: 10.1007/BF00606634. [DOI] [PubMed] [Google Scholar]
  12. Thorsson L., Dahlström K., Edsbäcker S., Källén A., Paulson J., Wirén J. E. Pharmacokinetics and systemic effects of inhaled fluticasone propionate in healthy subjects. Br J Clin Pharmacol. 1997 Feb;43(2):155–161. doi: 10.1046/j.1365-2125.1997.d01-1425.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Thorsson L., Edsbäcker S., Conradson T. B. Lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered-dose inhaler P-MDI. Eur Respir J. 1994 Oct;7(10):1839–1844. doi: 10.1183/09031936.94.07101839. [DOI] [PubMed] [Google Scholar]
  14. Wolthers O. D., Pedersen S. Measures of systemic activity of inhaled glucocorticosteroids in children: a comparison of urine cortisol excretion and knemometry. Respir Med. 1995 May;89(5):347–349. doi: 10.1016/0954-6111(95)90006-3. [DOI] [PubMed] [Google Scholar]
  15. Wolthers O. D., Pedersen S. Short-term growth during treatment with inhaled fluticasone propionate and beclomethasone dipropionate. Arch Dis Child. 1993 May;68(5):673–676. doi: 10.1136/adc.68.5.673. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES