What is the potency of oral budesonide compared to prednisone?

Oral Budesonide vs. Prednisone Potency Comparison

Oral budesonide has approximately 15 times the intrinsic potency of prednisolone (prednisone's active metabolite) at the glucocorticoid receptor, but due to its extensive first-pass hepatic metabolism (80-90%), it has significantly lower systemic bioavailability and fewer systemic side effects than prednisone. 1

Pharmacological Properties

Receptor Binding and Potency

• Budesonide has a high affinity for glucocorticoid receptors with an intrinsic potency approximately:
  • 200 times that of cortisol
  • 15 times that of prednisolone (prednisone's active metabolite) 1

Pharmacokinetics

• First-pass metabolism: Budesonide undergoes extensive (80-90%) first-pass hepatic metabolism 1
• Systemic bioavailability: Approximately 11% compared to prednisone's nearly complete absorption 2
• Metabolism: Primarily metabolized by CYP3A4 to two major metabolites (6β-hydroxy budesonide and 16α-hydroxy prednisolone) with negligible (<1/100) glucocorticoid activity 1

Clinical Implications

Efficacy Comparison

• In inflammatory bowel disease, budesonide (9 mg/day) has shown:
  • Similar clinical efficacy to prednisolone/prednisone in inducing remission 3, 4
  • Superior efficacy to placebo and mesalamine 2
  • In one study, prednisolone produced greater reduction in Crohn's Disease Activity Index scores compared to budesonide (279 to 136 vs. 275 to 175, p=0.001) 4

Side Effect Profile

• Significantly fewer glucocorticoid-related adverse effects with budesonide compared to prednisone 2, 3, 4
• Less suppression of the hypothalamic-pituitary-adrenal (HPA) axis compared to prednisone 4
• In clinical trials, budesonide had similar adverse event rates to placebo 2

Formulation Considerations

• Budesonide is available in different formulations:
  • Enteric-coated formulations (Entocort EC) designed to release in the ileum and ascending colon 2
  • MMX formulation with pH-dependent dissolution that delays release until exposure to pH ≥7 in the small intestine 1
  • These formulations enhance local anti-inflammatory effects while minimizing systemic absorption

Clinical Applications

• For mild to moderate ulcerative colitis:

  • Budesonide MMX is recommended as an alternative to systemic corticosteroids for patients who fail or cannot tolerate 5-ASA therapy 5
  • Prednisone remains the standard for moderate to severe disease 5

• For autoimmune hepatitis:

  • Budesonide may be considered as an alternative to prednisone in non-cirrhotic patients 5
  • Prednisone remains the mainstay of therapy in most cases 5

Important Caveats

• Budesonide's efficacy may be compromised in patients with:
  • Cirrhosis (due to altered first-pass metabolism) 5
  • Severe disease requiring potent systemic effects 5
• The high potency at the receptor level (15x prednisolone) is largely offset by the low systemic bioavailability in clinical practice

In summary, while budesonide has approximately 15 times the intrinsic potency of prednisolone at the receptor level, its extensive first-pass metabolism results in much lower systemic exposure, making it less potent systemically but with a significantly better side effect profile compared to prednisone.