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(Chest. 2000;117:1526.)
© 2000 American College of Chest Physicians

Absorption of High-Dose Inhaled Corticosteroids

Martin Brutsche-Carlen, MD; Ingrid Carlen-Brutsche, PhD and Ashley Woodcock, MD

Wythenshawe Hospital Manchester, England

Correspondence to: Ashley A. Woodcock, MD, Respiratory Physiology, Wythenshawe Hospital, South Moor Road, Manchester M23 9LT, England; e-mail: ashley{at}nwlung.u-net.com

To the Editor:

The appropriate and safe use of inhaled corticosteroids (ICS) is an important issue in managing asthma, and we read with interest the article by Wales et al (June 1999).1 This is now the seventh report showing increased adrenal suppression with very high doses of fluticasone propionate (FP) compared to budesonide (BUD) in volunteers.2 3 4 5 6 7 However, normal subjects do not generally receive these doses of ICS, and it is difficult to see the relevance of these studies to clinical practice.

Absorption of fluticasone is largely via the lung, and this is substantially reduced in asthmatics. We have recently compared plasma FP and cortisol levels after steady-state dosing with 1,000 µg FP (hydrofluorocarbon metered-dose inhaler via Volumatic Spacer; Glaxo Wellcome; Greenford, UK) in normal subjects and patients with moderately severe asthma (mean FEV1, 54% predicted). The area under curve (AUC) plasma FP was reduced by 62% and AUC plasma cortisol was significantly higher in the asthmatic subjects. This reduced systemic bioavailability in asthma would lend support to extensive clinical studies that show similar levels of adrenal suppression for FP and BUD at equal microgram dose in patients with asthma (summarized in Barnes et al9 ).

We would conclude that pharmocokinetic studies comparing drugs with different absorption pathways should be carried out in the patient group for which their use is intended, and not in normal volunteers where results can be misleading and open to misinterpretation. ICS remain the cornerstone of asthma management. However, irrespective of which specific ICS patients are taking, it is incumbent on health care professionals to treat asthmatics with the minimum dose compatible with good disease control. Patients must be "stepped down," and not left indefinitely on high-dose ICS, especially as lung function normalizes.

References

  1. Wales, D, Makker, H, Kane, J, et al (1999) Systemic bioavailability and potency of high-dose inhaled corticosteroids: a comparison of four inhaler devices and three drugs in healthy adult volunteers. Chest 115,1278-1284[Abstract/Free Full Text]
  2. Boorsma, M, Andersson, N, Larsson, P, et al (1996) Assessment of the relative systemic potency of inhaled fluticasone and budesonide. Eur Respir J 9,1427-1432[Abstract]
  3. Dogterom, P, Oosterhuis, B, Ebels, JT, et al (1995) Inhaled fluticasone propionate induces greater cortisol suppression compared to budesonide: a dose response study using pressurized metered dose inhalers (PMDI’S). Eur Respir J 8(suppl19),P1529
  4. Donnelly, R, Williams, KM, Baker, AB, et al (1997) Effects of budesonide and fluticasone on 24-hour plasma cortisol. Am J Respir Crit Car Med 156,1746-1751[Abstract/Free Full Text]
  5. Grahnen, A, Jansson, B, Brundin, RM, et al (1997) A dose-response study comparing suppression of plasma cortisol induced by fluticasone propionate from Diskhaler and budesonide from Turbuhaler. Eur J Clin Pharmacol 52,261-267[CrossRef][ISI][Medline]
  6. Grahnen, A, Eckernas, SA, Brundin, RM, et al (1994) An assessment of the systemic activity of single doses of inhaled fluticasone propionate in healthy volunteers. Br J Clin Pharmacol 38,521-525[ISI][Medline]
  7. Lonnebo, A, Grahnen, A, Jansson, B, et al (1996) 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 49,459-463[CrossRef][ISI][Medline]
  8. Brutsche-Carlen MH, Carlen-Beutsch I, Munavar M, et al. Pharmacokinetics and systemic effects of inhaled fluticasone propionate are different in asthmatics and normal volunteers. Lancet (in press)
  9. Barnes, NC, Hallett, C, Harris, TAJ (1998) Clinical experience with fluticasone propionate in asthma: a meta-analysis of efficacy and systemic activity compared with budesonide and beclomethasone dipropionate at half the microgram dose or less. Respir Med 92,95-104[CrossRef][ISI][Medline]




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