Skip to main content
PMC home page
Thorax logoLink to Thorax
. 1999 Jul;54(7):614–617. doi: 10.1136/thx.54.7.614

Evaluation of the buccal component of systemic absorption with inhaled fluticasone propionate

O Dempsey 1, W Coutie 1, A Wilson 1, P Williams 1, B Lipworth 1
PMCID: PMC1745527  PMID: 10377207

Abstract

BACKGROUND—Inhaled corticosteroids have dose related systemic effects determined by oral (swallowed or oropharyngeal absorption) and lung bioavailability. A study was undertaken to evaluate the significance of oropharyngeal absorption for fluticasone propionate.
METHODS—Sixteen healthy volunteers of mean age 29.3 years were studied using an open randomised, placebo controlled, four way crossover design. Treatments were: (a) fluticasone metered dose inhaler (pMDI) 250 µg, 8 puffs; (b) fluticasone pMDI 250 µg, 8 puffs +mouth rinsing/gargling (water); (c) fluticasone pMDI 250 µg, 8puffs + mouth rinsing/gargling (charcoal); and (d) placebo pMDI, 8 puffs + mouth rinsing/gargling (water). Overnight (ONUC) and early morning (EMUC) urinary cortisol/creatinine ratios and 8am serum cortisol (SC) levels were measured.
RESULTS—Significant (p<0.05) suppression of ONUC, EMUC, and SC occurred with each active treatment compared with placebo. The mean values (95% CI for difference from placebo) were: (a) ONUC (nmol/mmol): fluticasone (2.8, 95% CI 3.6 to 7.9), fluticasone + water (3.1,95% CI 3.3 to 7.7), fluticasone + charcoal (2.3, 95% CI 4.1 to 8.5); placebo (8.6); (b) EMUC (nmol/mmol): fluticasone (5.6, 95% CI 8.4 to 24.5), fluticasone + water (7.6, 95% CI 6.6 to 22.4); fluticasone + charcoal (5.6, 95% CI 8.7 to 24.5); placebo (22.1). There were no significant differences between active treatments. The numbers of subjects with an overnight urinary cortisol of <20 nmol/10 hours were 0 (placebo), 11 (fluticasone), 12 (fluticasone+ water), and 13 (fluticasone +charcoal).
CONCLUSIONS—Oropharyngeal absorption of fluticasone does not significantly contribute to its overall systemic bioactivity as assessed by sensitive measures of adrenal suppression. In view of almost complete hepatic first pass inactivation with fluticasone, there is no rationale to employ mouth rinsing to reduce its systemic effects although it may be of value for reducing oral candidiasis.



Full Text

The Full Text of this article is available as a PDF (89.7 KB).

Selected References

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

  1. 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]
  2. Harding S. M. The human pharmacology of fluticasone propionate. Respir Med. 1990 Nov;84 (Suppl A):25–29. doi: 10.1016/s0954-6111(08)80004-2. [DOI] [PubMed] [Google Scholar]
  3. Johnson M. Development of fluticasone propionate and comparison with other inhaled corticosteroids. J Allergy Clin Immunol. 1998 Apr;101(4 Pt 2):S434–S439. doi: 10.1016/s0091-6749(98)70155-1. [DOI] [PubMed] [Google Scholar]
  4. Lipworth B. J. New perspectives on inhaled drug delivery and systemic bioactivity. Thorax. 1995 Feb;50(2):105–110. doi: 10.1136/thx.50.2.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Lipworth B. J. Pharmacokinetics of inhaled drugs. Br J Clin Pharmacol. 1996 Dec;42(6):697–705. doi: 10.1046/j.1365-2125.1996.00493.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Lipworth B. J., Seckl J. R. Measures for detecting systemic bioactivity with inhaled and intranasal corticosteroids. Thorax. 1997 May;52(5):476–482. doi: 10.1136/thx.52.5.476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Martin L. E., Harrison C., Tanner R. J. Metabolism of beclomethasone dipropionate by animals and man. Postgrad Med J. 1975;51 (Suppl 4):11–20. [PubMed] [Google Scholar]
  8. McIntyre H. D., Mitchell C. A., Bowler S. D., Armstrong J. G., Wooler J. A., Cowley D. M. Measuring the systemic effects of inhaled beclomethasone: timed morning urine collections compared with 24 hour specimens. Thorax. 1995 Dec;50(12):1280–1284. doi: 10.1136/thx.50.12.1280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ryrfeldt A., Andersson P., Edsbäcker S., Tönnesson M., Davies D., Pauwels R. Pharmacokinetics and metabolism of budesonide, a selective glucocorticoid. Eur J Respir Dis Suppl. 1982;122:86–95. [PubMed] [Google Scholar]
  10. Selroos O., Halme M. Effect of a volumatic spacer and mouth rinsing on systemic absorption of inhaled corticosteroids from a metered dose inhaler and dry powder inhaler. Thorax. 1991 Dec;46(12):891–894. doi: 10.1136/thx.46.12.891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Wilson A. M., Lipworth B. J. 24 hour and fractionated profiles of adrenocortical activity in asthmatic patients receiving inhaled and intranasal corticosteroids. Thorax. 1999 Jan;54(1):20–26. doi: 10.1136/thx.54.1.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Wilson A. M., McFarlane L. C., Lipworth B. J. Dose-response effect for adrenal suppression with repeated twice daily inhaled fluticasone propionate and triamcinolone acetonide in adult asthmatics. Am J Respir Crit Care Med. 1997 Oct;156(4 Pt 1):1274–1277. doi: 10.1164/ajrccm.156.4.97-03029. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES