Systemic Bioavailability and Potency of High-Dose Inhaled Corticosteroids: Discussion
Inhaled corticosteroids in low and medium doses are safe with regard to systemic side effects; to our knowledge, there are no reported cases of clinically relevant adrenal suppression within the licensed dose range. However, when higher doses are employed to control asthma symptoms, adrenal suppression becomes a possibility. We used a model system of a single high dose of inhaled corticosteroid in normal volunteers. It is unlikely that any physician would prescribe a 4-mg dose of inhaled corticosteroid, but this ultrahigh dose allowed us to make a comparison of drugs and devices that would be very difficult to make with low doses of inhaled steroids due to the high “signal to noise” ratio. A possible weakness of our study is that we have used such high (unlicensed) doses of inhaled corticosteroids in normal volunteers read online antibiotics. It is likely that the lung deposition, pharmacokinetics, and pharmacodynamics of the inhaled drugs would be different if low doses of inhaled steroids were given to asthmatic subjects with narrow, inflamed airways and mucus plugs, However, although the absolute effect might be different in asthmatic subjects, there is no reason to believe that the relative effects of the drugs and devices would be significantly different in asthmatic subjects compared with normal control subjects.
For example, the study of Agertoft and Pederson suggested that the budesonide Turbohaler had twice the therapeutic potency of budesonide given by MDI spacer device to asthmatic children, and the authors suggested that the Turbohaler device may deliver twice as much steroid to the lungs. This is consistent with the approximate 2:1 systemic potency ratio for these devices in the present study. Furthermore, the relative systemic potency of fluticasone to budesonide in the present study (slightly > 2:1 potency at equal microgram doses) is similar to the reported therapeutic potency of these agents when given in repeated doses to asthmatic subjects. Our systemic potency ratio (fluticasone to budes-onide > 2:1) is almost identical to that of Clark and Lipworth who studied the dose response curves for cortisol suppression when twice-daily doses of budesonide and fluticasone were given to asthmatic subjects for 4 days.