Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Corticosteroids for systemic use, pure, glucocorticoids, betamethasone
ATC Code: H02AB01
Betamethasone is a mono-fluorinated glucocorticoid, which has an approximately 25-fold more potent anti-inflammatory effect than the natural adrenal hormone cortisol. The mineralocorticoid effect-component is however almost completely absent.
Glucocorticoids such as betamethasone develop their biological effect by activating the transcription of corticosteroid-sensitive genes. The anti-inflammatory, immunosuppressive and antiproliferative effects are caused for example by reduced formation, release and activity of inflammatory mediators and by inhibition of specific functions and migration of inflammatory cells. In addition, corticosteroids may prevent the effect of sensitised T- lymphocytes and macrophages on target cells.
Glucocorticoids such as betamethasone promote surfactant synthesis in the foetal lung.
Possible induction of temporary adrenal insufficiency must be taken into account with necessary long-term corticosteroid medication. Suppression of the hypothalamus-pituitary- adrenal axis also depends on individual factors.
The Cushing’s threshold dose is specified at 1.5 mg / day.
Betamethasone is a glucocorticoid which is 8 to 10 times more active than prednisolone (based on weight; 750µg betamethasone corresponding to approximately 5 mg prednisolone).
Betamethasone sodium phosphate is highly soluble in water and is therefore quickly absorbed.
Betamethasone usually only causes poor retention of sodium chloride or water. Due to lack of mineralocorticoid properties betamethasone is particularly suitable for the treatment of diseases where water retention is adversely affected.

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
Betamethasone sodium phosphate is hydrolysed in the body to the biologically active form betamethasone, reaches the highest blood levels within 60 minutes and is excreted almost entirely after the first day.
Corticosteroids are in general absorbed liberally in the gastrointestinal tract, bound to plasma proteins in varying degrees, primarily metabolised in the liver and excreted by the kidneys.
Corticosteroids are rapidly distributed in all body tissues. They cross the placenta to varying degrees and small quantities may be distributed into breast milk. The (serum) elimination half-life of betamethasone in adults is approximately 5-7 hours.
Betamethasone has a protein binding of 62.5% (compared to hydrocortisone 89%).
While the plasma half-life of betamethasone is ≥300 minutes, the biological half-life was identified as 36-54 hours. Due to the long duration of action, betamethasone hence may lead, with daily continuous administration, to continuous accumulation and overdose. In patients with liver disease degradation is slower.
When betamethasone sodium phosphate was used infiltratively in healthy volunteers, a negative feedback mechanism on the hypothalamic-pituitary system lead to suppression of the cortisol plasma level within approximately 8-10 hours. This was normalised within a few days.