Betamethasone metabolism

Betamethasone is hardly ever used orally. It has a long duration of activity and can therefore also be used for alternate-day therapy. The parenteral formulation is also the sodium phosphate salt which when given IV or IM has a rapid onset of action. There are many similarities with dexamethasone such as their metabolic pathways and the indications for which both steroids are used, like the prevention of neonatal RDS and reduction of raised intracranial pressure. Combinations of betamethasone acetate and sodium phosphate have, when used for intra-articular and intra-lesional injections, the dual advantage of a rapid onset of action together with the long duration of action of a depot preparation. 

Inhaled glucocorticoid preparations, such as be-clomethasone dipropionate and betamethasone valerate, provide an effective alternative to systemic steroids in the treatment of chronic asthma, with lesser side effects than oral or parenteral glucocorticoids (see Chapter 39). In fact, inhaled glucocorticoids have become a mainstay of asthma therapy. Inhalation delivers the agent directly to the target site in relatively low doses, with the potential for more frequent administration. Moreover, inhaled glucocorticoids are metabolized in the lung before they are absorbed, which reduces their systemic effects. However, even modest doses of... 

Lung maturation in the fetus is regulated by the fetal secretion of cortisol. Treatment of the mother with large doses of glucocorticoid reduces the incidence of respiratory distress syndrome in infants delivered prematurely. When delivery is anticipated before 34 weeks of gestation, intramuscular betamethasone, 12 mg, followed by an additional dose of 12 mg 18-24 hours later, is commonly used. Betamethasone is chosen because maternal protein binding and placental metabolism of this corticosteroid is less than that of cortisol, allowing increased transfer across the placenta to the fetus. 

Betamethasone is well absorbed after oral administration to be extensively bound to plasma proteins in humans, dogs, cows, and rats. Its metabolism does not differ of the other corticosteroids, involving oxidation of the 11 -hydroxyl group to ketone, reduction of the ketone group at the position C-20 to give the corresponding alcohol, and hydroxylation at the C-6 position and loss of the C-17 side chain to give 17-oxosteroids. 

Betamethasone is a corticosteroid. Corticosteroids are very lipophilic (due to their hydrocarbon skeleton) and as a result can passively diffuse into target cells. It acts by binding to the intracellular corticosteroid receptor protein, which is found within the cytosol. The resulting complex translocates to the nucleus and induces synthesis of mediator proteins (e.g. metabolic enzymes and lipocortin). The binding of steroid hormones to their receptors causes changes in gene transcription and cell function. Corticosteroids reduce the inflammatory reaction by limiting capillary dilatation and vascular permeability. 

CORTICOSTEROIDS PROTEASE INHIBITORS-RITONAVIR t plasma levels of betamethasone, dexamethasone, hydrocortisone, prednisolone and both inhaled and intranasal budesonide and fluticasone with ritonavir (with or without lopinavir) Inhibition of CYP3A4-mediated metabolism Monitor closely for signs of corticosteroid toxicity and immunosupression, and i dose as necessaiy. Consider using inhaled bedometasone... 

Jonsson, G. Astrom, A Andersson, P. Budesonide is metabolized by cytochrome P450 3A (CYP3A) enzymes in human liver. Drug Metab.Dispos., 1995, 23, 137-142 [human hver microsomal incubations extracted budesonide betamethasone is IS SPE gradient]... 

The elimination half-life of theophylline (given as intravenous aminophyl-line) was no different in premature infants who had been exposed to betamethasone in utero than in those who had not, although the exposed neonates had a wider range of theophylline metabolites indieating greater hepatie metabolism. ... 

Jager-Roman E, Doyle PE, Thomas D, Baird-Lambert J, Cvejic M, Buchanan N. Increased theophylline metabolism in premature infants after prenatal betamethasone administration. 

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