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  • Title: Clinical pharmacology of corticosteroids in bronchial asthma.
    Author: Lipworth BJ.
    Journal: Pharmacol Ther; 1993; 58(2):173-209. PubMed ID: 8415878.
    Abstract:
    It is now recognised that suppression of the inflammatory cascade should be the cornerstone of management in bronchial asthma. Inhaled corticosteroids are the most effective and widely used form of anti-inflammatory therapy for use in patients with asthma. The limited data available on dose-response relationships for inhaled corticosteroids suggest that a plateau occurs for antiasthmatic efficacy above 1600 micrograms either for budesonide and beclomethasone dipropionate with no appreciable differences between the two drugs. However, in most cases it should be possible to achieve adequate asthma control with doses of either drug less than 1000 micrograms with a use of an optimal inhaler device and good compliance. In contrast to topical anti-inflammatory activity in airways, for both local and systemic adverse effects there is a steep dose-response above 1600 micrograms with budesonide and beclomethasone dipropionate. In comparison with oral prednisolone there is still a better risk-benefit ratio even with higher doses of inhaled corticosteroids. There is evidence to suggest that inhaled budesonide may have a slightly more favourable profile in terms of the ratio of topical to systemic activity, particularly for effects on bone metabolism. A significant degree of adrenal suppression is unlikely at doses less than 1600 micrograms of budesonide or beclomethasone, although there is a degree of interindividual variability in the dose-response relationship for this effect, as well as for antiasthmatic activity. Thus, doses of inhaled corticosteroid should be titrated on an individual basis in order to achieve adequate disease control. At doses in excess of 800 micrograms it would seem rational to use a large volume spacer device since this will lessen local adverse effects such as oral candidiasis and dysphonia, as well as reducing systemic absorption and improving lung deposition. Mouth washing may reduce local and systemic adverse effects when using dry powder devices at high doses. Another possible strategy to improve efficacy with higher doses is to increase the dosing frequency from twice to four times daily, although this may at the same time produce an increase in local adverse effects. Fluticasone propionate is a novel inhaled corticosteroid with very high topical anti-inflammatory activity and minimal systemic bioavailability and might, therefore, provide a favourable therapeutic profile at the high end of the dose range. The next decade of research into the clinical pharmacology of inhaled corticosteroids is, therefore, eagerly awaited and will hopefully consolidate improvements in asthma management with this important class of anti-inflammatory drugs.
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