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Absorption of high-dose inhaled corticosteroids.

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.2–7 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 mg 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.