Figure 2. Factors increasing the systemic bioavailability of
glucocorticoids administered topically or by inhalation
Absorption of the drug from the site of administration is greater if
drug molecules are lipophilic and soluble or formulated with a vehicle
with solvent or occlusive properties, which increase epithelial
permeability. It is also greater with higher dosage, application over
greater surface area, and in underlying disease e.g. where there is
inflammation increasing epithelial permeability.
In the plasma, glucocorticoids are bound to corticosteroid-binding
globulin (transcortin) and albumin. Factors that reduce these proteins,
such as disease states with increased protein loss or decreased
synthesis, could increase free circulating glucocorticoids.
Interactions with drugs that inhibit the hepatic enzymes that clear
glucocorticoids (e.g. cyclosporin, erythromycin, itraconazole and
ritonavir) or induce hepatic enzymes that activate glucocorticoid
prodrugs can increase systemic exposure to glucocorticoids. Systemic
exposure is also increased if glucocorticoid clearance is reduced e.g.
by hepatic or renal impairment, and by hypothyroidism and older age