Entocort Mechanism of Action





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Pharmacotherapeutic group: Glucocorticosteroid for local treatment. ATC-code: A07EA06.
Pharmacology: Pharmacodynamics: The mechanism of action of glucocorticosteroids in the treatment of Crohn's disease is not fully understood. Anti-inflammatory effect such as inhibition of the release of inflammatory mediators and inhibition of cytokine mediated immunological defence is probably of significance.
Clinical data indicate that Entocort have high local anti-inflammatory effects. Compared with prednisolone 40 mg, Entocort gives an equivalent frequency of clinical remission in patients with mild to moderate disease (CDAI score <300), but in recommended doses significantly less effect on the HPA-axis (both for the morning plasma cortisol value, and the 24-hour plasma and urinary cortisol values) and on systemic inflammatory markers, blood glucose and serum alkaline phosphatase.
At the recommended dosage, ACTH tests have shown significantly less effect on adrenal function than after treatment with prednisolone 40 mg.
In a subgroup analysis, in steroid naive patients, investigating bone mineral density during treatment with Entocort or prednisolone for two years, treatment with Entocort resulted in significantly less bone loss than prednisolone. In previously treated patients there was no difference between the groups.
Pharmacokinetics: Absorption: After oral intake of pure, micronised budesonide the absorption is rapid and it is apparently complete. After dosage of Entocort capsules, uptake of the major part of the absorbed drug takes place in the ileum and in the ascending colon. In patients with active Crohn's disease the bioavailability after a single dose is 12-20%. In healthy persons the corresponding value is 9-12%.
Distribution: Budesonide has a volume of distribution of about 3 L/kg. The protein binding in plasma is as a mean 85-90%. After an oral dose of 9 mg budesonide as Entocort capsules the mean peak plasma concentration is approximately 5-10 nmol/L, obtained after 3-5 hours.
Biotranformation: Budesonide undergoes an extensive degree (about 90%) of biotransformation on first passage through the liver to metabolites with low glucocorticoid activity. The glucocosteroid activity of the main metabolites, 6-beta-hydroxybudesonide and 16-alpha-hydroxyprednisolone, is less than 1% of that of budesonide. The metabolism of budesonide is primarily mediated by CYP3A, a subfamily of cytochrome 450.
Elimination: The elimination rate of budesonide given as Entocort capsules is controlled by the absorption, and the half-life in plasma is approximately 4 hours. The metabolites are excreted unchanged or as conjugates, primarily though the kidneys. No intact budesonide has been detected in the urine. Budesonide has a high systemic clearance (approximately 1.2 L/min), and the mean half-life in plasma after intravenous administration is 2-3 hours.
The kinetics of budesonide are proportional to the dose in the therapeutic dosage range.
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