We believe, therefore, that the relative potency of drugs and devices that we found in normal volunteers who received single high doses of steroids is very similar to the relative potency of the same drugs and devices when inhaled steroids are given to asthmatic subjects in repeated doses. However, the absolute effects are probably different, as healthy subjects with normal airways receive higher doses to the lungs than asthmatic subjects. This has been shown for inhaled salbutamol (1.5:1 ratio for lung deposition in normal subjects vs asthmatic subjects) and for inhaled fenoterol (2:1 ratio for plasma fenoterol level). No similar information is available for inhaled steroids, but the 72% suppression of plasma cortisol in normal volunteers by 2 mg of fluticasone (by MDI spacer) in the present study compared with 58% suppression in the study of Tan and Lipworth (using MDI alone) in patients with mild asthma and would imply a ratio of at least 1.2:1 for normal subjects compared with asthmatic patients.
In the present study, we first looked at the effects of different delivery devices on serum cortisol levels when a single high dose of budesonide was administered. We found that systemic bioavailability was significantly influenced by the choice of delivery system itat on birth control. Most of the bioavailability of inhaled corticosteroids is through absorption in the lung.2This has been shown in previous studies by Pederson et al who assessed the effects of mouth rinsing with activated charcoal and Selroos and Halme who employed mouth rinsing with water and showed a reduction in systemic effects (due to GI absorption) of only 15 to 20%. In our study, high-dose oral budesonide produced a modest 14% suppression of 9:00 am cortisol level, in keeping with the results of the above studies. By comparison, high-dose inhaled budesonide caused up to 73% suppression of plasma cortisol in the present study, confirming that the systemic effect is mostly due to pulmonary, not GI, absorption. However, we cannot exclude the possibility that the GI absorption of the preparation that we used (Pulmicort Respules) may be different from that of the MDI preparation.
Category: Inhaled Corticosteroids
Tags: adrenal suppression, beclomethasone dipropionate, bioavailability, budesonide, fluticasone propionate, inhaled corticosteroids