Systemic Bioavailability and Potency of High-Dose Inhaled Corticosteroids
A Comparison of Four Inhaler Devices and Three Drugs in Healthy Adult Volunteers
Inhaled steroids are used extensively in the man agement of asthma. Sometimes high doses (> 1,500 ^g/d) are necessary to control symptoms. Systemic effects such as suppression of the hypothalamic-pituitary-adrenal (HPA) axis can occur at these high doses; however, there are few reports of clinically important systemic effects from these drugs.
The therapeutic goal should be to optimize asthma control but to minimize potential systemic side effects. Anti allergy medicine more It is known that the choice of inhaler device can influence lung deposition (and systemic bioavailability) of inhaled corticosteroids, but the relative effects of various inhaler devices, spacer devices, nebulizers, and dry powder devices are poorly un-derstood.
In this study, two experiments were performed. The first experiment was to compare the relative effectiveness of several delivery techniques using a single steroid as a marker. Budesonide was taken via four different inhaler devices (metered-dose inhaler [MDI] alone, MDI and large volume spacer, dry powder device, and nebulizer) and the systemic bioavailability was determined by measuring suppression of 9:00 am plasma cortisol level. The second experiment was to compare the relative potency of three inhaled steroids when given by MDI and spacer. Fluticasone, beclomethasone dipropionate, and budesonide were taken by large volume spacer, the preferred delivery system for high-dose steroids and suppression of 9:00 am plasma cortisol level was measured.
Systemic bioavailability is largely determined by lung deposition and absorption. Previous studies of this nature have yielded conflicting results because low or moderate doses of inhaled steroids were administered producing only modest falls in morning cortisol levels with a high “signal to noise” ratio. For this reason, we used very high doses of inhaled steroid (4 mg) to ensure that any difference between drugs and devices would be demonstrated clearly.