Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1        Pharmacodynamic properties
ATC Code: A11C C03 (Vitamin A and D, incl. combinations of the two, vitamin D and analogues).

Alfacalcidol is converted rapidly in the liver to 1,25dihydroxyvitamin 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 Alpha D3 and 1,25- dihydroxyvitamin D are very similar.

When 1-α hydroxylation by the kidneys is impaired, endogenous 1,25- dihydroxyvitamin D3 production is reduced. Disorders in which this can occur include renal bone disease, hypoparathyroidism, neonatal hypocalcaemia and Vitamin D-dependent rickets. Such conditions require high doses of Vitamin D for their correction but will respond to small doses of Alpha D3, which does not depend on the renal 1-α hydroxylation process.

When using parent Vitamin D, the high dose and variable response time makes dosage adjustment difficult. This can lead to unpredictable hypercalcaemia which may take many weeks, sometimes months, to reverse.
With Alpha D3, the more rapid onset of response allows better titration of dose and, if hypercalcaemia does occur, it can be reversed within days of stopping treatment.

Pharmacokinetic Properties

5.2        Pharmacokinetic properties

Alfacalcidol undergoes rapid hepatic conversion to 1,25-dihydroxy-vitamin D3, the Vitamin D3 metabolite which acts as a regulator of calcium and phosphate metabolism.
In patients with renal failure, 1-5 μg/day of 1α-hydroxyvitamin D (1α-OHD3) increased intestinal calcium and phosphorus absorption in a dose-related manner. This effect was observed within 3 days of starting the drug and conversely, it was reversed within 3 days of its discontinuation.

In patients with nutritional osteomalacia, increases in calcium absorption were noted within 6 hours of giving 1 μg 1α-OHD3 orally and usually peaked at 24 hours. 1α-OHD3 also produced increases in plasma inorganic phosphorus due to increased intestinal absorption and renal tubular re-absorption. This latter effect is a result of PTH suppression by 1α-OHD3. The effect of the drug on calcium was about double its effect on phosphorus absorption.

Patients with chronic renal failure have shown increased serum calcium levels within 5 days of receiving 1α-OHD3 in a dose of 0.5 -1.0 μg/day. As serum calcium rose, PTH levels and alkaline phosphatase decreased toward normal.