What is the bioavailability of oral budesonide?

Oral Budesonide Bioavailability

Oral budesonide has a low bioavailability of approximately 10-15% due to extensive first-pass metabolism in the liver, which is its key therapeutic advantage in inflammatory bowel disease and autoimmune hepatitis. 1

Pharmacokinetic Profile

Budesonide is a potent corticosteroid with unique pharmacokinetic properties that make it valuable for treating various inflammatory conditions while minimizing systemic side effects:

• First-pass metabolism: Following absorption, budesonide undergoes high first-pass metabolism (80-90%) in the liver 1
• Metabolism pathway: Primarily metabolized by CYP3A4 to two major metabolites (6β-hydroxy budesonide and 16α-hydroxy prednisolone) 1
• Metabolite activity: The glucocorticoid activity of these metabolites is negligible (<1/100) compared to the parent compound 1
• Plasma clearance: High plasma clearance (0.9-1.8 L/min), approaching estimated liver blood flow 1
• Half-life: Plasma elimination half-life ranges between 2 and 3.6 hours 1
• Excretion: Excreted in urine and feces as metabolites, with approximately 60% of recovered radioactivity found in urine 1

Clinical Implications

The low systemic bioavailability of oral budesonide offers significant clinical advantages:

1. Reduced systemic effects: Compared to conventional corticosteroids like prednisolone, budesonide causes fewer glucocorticoid-related adverse effects 2

2. Targeted delivery: Different formulations target specific areas of the GI tract:

   • Entocort EC: Designed to release in the ileum and ascending colon 2
   • Budesonide MMX: Designed for release throughout the colon 3

3. Adrenal suppression: Despite lower systemic exposure, adrenal suppression can still occur:

   • In one study, abnormal response to ACTH stimulation was seen in 47% of patients at 4 weeks and 79% at 8 weeks 1

Special Populations

Hepatic Impairment

• In patients with liver cirrhosis, systemic availability of oral budesonide correlates with disease severity
• On average, bioavailability is 2.5-fold higher compared to healthy controls 1
• Patients with mild liver disease are minimally affected 1
• Caution: Budesonide should be used with caution in patients with hepatic impairment due to potentially increased systemic exposure

Drug Interactions

• CYP3A4 inhibitors: Potent inhibitors can increase plasma levels of budesonide several-fold
  • Ketoconazole: Eight-fold increase in AUC 1
  • Grapefruit juice: Approximately doubles systemic exposure 1
• CYP3A4 inducers: Can result in lowering of budesonide plasma levels 1

Clinical Applications

Budesonide's unique pharmacokinetic profile makes it particularly valuable in:

• Inflammatory bowel disease: Effective for induction of remission in mild to moderate ulcerative colitis and Crohn's disease 3
• Autoimmune hepatitis: Used as an alternative to conventional corticosteroids, especially in patients intolerant to standard therapy 3

Common Pitfalls

1. Assuming complete absence of systemic effects: Despite low bioavailability, systemic effects can still occur, especially with prolonged use

2. Using in severe hepatic impairment: Patients with cirrhosis may have significantly increased systemic exposure 1

3. Overlooking drug interactions: Concurrent use of CYP3A4 inhibitors can substantially increase systemic exposure 1

4. Using for maintenance therapy in UC: Guidelines recommend against using corticosteroids including budesonide for maintenance therapy in UC due to lack of efficacy and potential for adverse effects 3