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