Correspondence to: Ashley A. Woodcock, MD, Respiratory Physiology, Wythenshawe Hospital, South Moor Road, Manchester M23 9LT, England; e-mail: firstname.lastname@example.org
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).1This 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 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.
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