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Pharmacotherapeutic group: Vitamin D and analogues. ATC code: A11CC05.
Pharmacology: Pharmacodynamics: In its biological active form vitamin D3 stimulates intestinal calcium absorption, incorporation of calcium into the osteoid, and release of calcium from bone tissue. In the small intestine it promotes rapid and delayed calcium uptake. The passive and active transport of phosphate is also stimulated. In the kidney, it inhibits the excretion of calcium and phosphate by promoting tubular resorption. The production of parathyroid hormone (PTH) in the parathyroids is inhibited directly by the biologically active form of vitamin D3. PTH secretion is inhibited additionally by the increased calcium uptake in the small intestine under the influence of biologically active vitamin D3.
Pharmacokinetics: The pharmacokinetics of vitamin D is well known. Vitamin D is well absorbed from the gastro-intestinal tract in the presence of bile. It is hydroxylated in the liver to form 25-hydroxycolecalciferol and then undergoes further hydroxylation in the kidney to form the active metabolites circulate in the blood bound to a specific α-globin. Vitamin D and its metabolites are excreted mainly in the bile and faeces.
Toxicology: Preclinical safety data: Vitamin D is well known and is a widely used material and has been in clinical practice for many years. As such toxicity is only likely to occur in chronic overdosage where hypercalcaemia could result.
Colecalciferol has been shown to be teratogenic in high doses in animals (4-15 times the human dose). Offspring from pregnant rabbits treated with high dose of vitamin D had lesions anatomically similar to those of supravalvular aortic stenosis and offspring not showing such changing show vasculotoxicity similar to that of adults following acute vitamin D toxicity.
