Pharmacology and pharmacokinetics of topical corticosteroid derivatives used for asthma therapy.

Although systemic corticosteroids provide additional therapeutic benefit for persons with refractory asthma, their side effects make them less than optimal agents. Introduction of beclomethasone dipropionate (BDP), the first corticosteroid that is clinically useful when delivered by aerosol, provided a major advance in asthma therapy. Patients who were previously maintained on daily systemic steroids could be transferred to inhaled steroids with no loss of medical benefit and significant improvement in the function of the hypothalamic-pituitary-adrenal axis. The value of BDP and subsequent topical corticosteroids lies in their pharmacologic properties. These agents possess increased intrinsic potency when administered by inhaler. At the same time they have considerably lower systemic potency than corticosteroids such as hydrocortisone and dexamethasone in aerosol form. This is because the fraction of the topically useful compounds that is swallowed, which is substantial, is rapidly inactivated by first-pass metabolism in the liver. Absorption of unmetabolized drug through the pulmonary circulation accounts for most of the systemic effect of topical corticosteroids. Use of spacers in the aerosol delivery device can further increase the efficacy of these substances, or allow lowering of the dose.