Comprehensive Monograph: Hydrocortisone Acetate (DB14539)

1.0 Executive Summary

Hydrocortisone acetate (DrugBank ID: DB14539; CAS Number: 50-03-3) is a synthetic corticosteroid, specifically the acetate ester of the endogenous glucocorticoid hormone cortisol.[1] First approved for clinical use in 1951, it has remained a cornerstone of therapy for over seven decades due to its potent anti-inflammatory and immunosuppressive properties.[1] As a small molecule drug, its therapeutic action is mediated through a well-defined molecular mechanism. Upon cellular entry, hydrocortisone acetate binds to and activates the cytoplasmic glucocorticoid receptor (GR). The activated drug-receptor complex translocates to the nucleus, where it modulates gene expression through both transactivation of anti-inflammatory genes (e.g., Annexin A1) and transrepression of pro-inflammatory genes (e.g., those encoding cytokines and chemokines).[1] A key downstream effect is the inhibition of phospholipase A2, which blocks the arachidonic acid cascade and prevents the synthesis of inflammatory mediators such as prostaglandins and leukotrienes.[1]

The clinical utility of hydrocortisone acetate is exceptionally broad, a versatility driven largely by formulation science that tailors its pharmacokinetic profile for specific therapeutic goals. It is available in a wide array of formulations, including topical creams and ointments for corticosteroid-responsive dermatoses, systemic oral tablets and injectable suspensions for adrenal insufficiency and severe inflammatory or autoimmune disorders, and rectal foams and suppositories for localized inflammatory bowel diseases like ulcerative colitis.[5]