Kalsidol Mechanism of Action

Pharmacology: PHARMACODYNAMICS: Summary of Product Characteristics: Alfacalcidol is converted rapidly in the liver to 1,25-dihydroxyvitamin D. This is the metabolite of vitamin D which acts as a regulator of calcium and phosphate metabolism. Since this conversion is rapid, the clinical effects of Alfacalcidol and 1,25-dihydroxyvitamin D are very similar. Impaired 1-α hydroxylation by the kidneys reduces endogenous 1,25-dihydroxyvitamin D production. This contributes to the disturbances in mineral metabolism found in several disorders, including renal bone disease and hypoparathyoidism. These disorders, which require high doses of parent vitamin D for their correction, will respond to small doses of Alfacalcidol. The delay in response and high dosage required in treating these disorders with parent vitamin D makes dosage adjustment difficult. This can result in unpredictable hypercalcaemia which may take weeks or months to reverse. The major advantage of Alfacalcidol is the more rapid onset of response, which allows a more accurate titration of dosage. Should inadvertent hypercalcaemia occur it can be reversed within days of stopping treatment.
PHARMACOKINETICS: Vitamin D substance are well absorbed from the gastrointestinal tract. The presence of bile is essential for adequate intestinal absorption, absorption may be decreased in patients with decreased fat absorption.
Vitamin D and its metabolites circulate in the blood bound to a specific α-globulin. Vitamin D can be stored in adipose and muscle tissue for long periods of time. It is slowly released from such storage sites and from the skin where it is formed in the presence of sunlight or ultraviolet light. Ergocalciferol and colecalciferol have a slow onset and a long duration of action: calcitriol and its analogue alfacalcidol, however, have a more rapid action and shorter half-lives.
Colecalciferol and ergocalciferol are hydroxylated in the liver by the enzyme vitamin D 25-hydroxylase to form 25-hydroxycholecalciferol (calcifediol) and 25-hydroxyergocalciferol respectively. These compounds undergo further hydroxylation in the kidneys by the enzyme vitamin D 1-hydroxylase to form the active metabolites 1,25-dihydroxycholecalciferol (calcitriol) and 1,25-dihydroxyergocalciferol respectively. Further metabolism also occurs in the kidneys, including the formation of the 1,24,25-trihydroxy derivatives. Of the synthetic analogues, alfacalcidol, dihydrotachysterol, and doxercalciferol are converted directly in the liver to their active metabolites (calcitriol, 25-hydroxydihydrotachysterol, and 1,25-dihydroxyergocalciferol respectively).
Vitamin D compounds and their metabolites are excreted mainly in the bile and faeces with only small amounts appearing in urine: there is some enterohepatic recycling but it is considered to have a negligible contribution to vitamin D status. Certain vitamin D substances may be distributed into breast milk.