Singapore Drugs Database

Indication

The oral capsule is used for the treatment of mild to moderate active Crohn's disease. The oral tablet is used for induction of remission in patients with active, mild to moderate ulcerative colitis. The oral inhalation formulation is used for the treatment of asthma, non-infectious rhinitis (including hay fever and other allergies), and for treatment and prevention of nasal polyposis.

Mechanism of Action

Budesonide is an anti-inflammatory corticosteroid that exhibits potent glucocorticoid activity and weak mineralocorticoid activity. The precise mechanism of corticosteroid actions on inflammation in asthma, Crohn's disease, or ulcerative colitis is not known. Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have been shown to have a wide range of inhibitory activities against multiple cell types (eg, mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (eg, histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic and non-allergic-mediated inflammation. These anti-inflammatory actions of corticosteroids may contribute to their efficacy in the aforementioned diseases. Because budesonide undergoes significant first-pass elimination, the both oral preparations are formulated as an extended release tablet. As a result, budesonide release is delyaed until exposure to a pH ≥ 7 in the small intestine.

Pharmacokinetics

Absorption

Absorption is complete following oral administration. The pharmacokinetic parameters of the inhaled powder formulation are as follows: Tmax = 30 minutes; Absolute systemic availability = 39%. When a single oral administration of 9 mg of Uceris are given, the pharmacokinetic parameters are as follows: Tmax = 13.3 ± 5.9 hours; Cmax = 1.35 ± 0.96 ng/mL; AUC = 16.43 ± 10.52 ng·hr/mL. It is important to note that the parameters have a high degree of variability. When a single oral administration of Entocort EC are given, the pharmacokinetic parameters are as follows: Tmax = 3- 600 minutes; Cmax = 5 nmol/L; AUC = 30 nmol•hr/L.

Distribution

Tablet and capsule, healthy subjects and patients = 2.2 - 3.9 L/kg; Powder, metered = 3 L/kg

Metabolism

Following absorption, budesonide is subject to high first pass metabolism (80-90%). Budesonide is rapidly and extensively biotransformed, mainly by CYP3A4, to its 2 major metabolites, 6b-hydroxybudesonide and 16a- hydroxyprednisolone. The glucocorticoid activity of these metabolites is negligible (

Elimination

Clearance

Plasma clearance, tablet = 0.9 - 1.8 L/min; Systemic clearance, powder, 22R = 1.4 L/min; Systemic clearance, powder, 22S = 1.0 L/min; 0.5 L/min [Athmatic children 4 to 6 years of age]

Toxicity

Single oral doses of 200 and 400 mg/kg were lethal in female and male mice, respectively. The signs of acute toxicity were decreased motor activity, piloerection and generalized edema.

Active Ingredient/Synonyms

(11beta,16alpha)-16,17-(Butylidenebis(oxy))-11,21-dihydroxypregna-1,4-diene-3,20-dione | Budesonide |