| Candidate ID: | R0523 |
| Source ID: | DB01436 |
| Source Type: | approved; nutraceutical |
| Compound Type: |
small molecule
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| Compound Name: |
Alfacalcidol
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| Synonyms: |
(5Z,7E)-9,10-seco-5,7,10(19)-cholestatrien-1α,3β-diol; 1-hydroxycholecalciferol; 1alpha-hydroxycholecalciferol; 1α-hydroxy-vitamin D3; 1α-hydroxycholecalciferol; 1α-hydroxyvitamin D3; 9,10-secocholesta-5,7,10(19)-triene-1α,3β-diol
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| Molecular Formula: |
C27H44O2
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| SMILES: |
CC(C)CCC[C@@H](C)[C@@]1([H])CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C
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| Structure: |
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| DrugBank Description: |
Alfacalcidol, or 1-alpha-hydroxycholecalciferol or 1-alpha-hydroxyvitamin D3, is a non-endogenous analogue of . It plays an essential function in calcium homeostasis and bone metabolism. Alfacaldisol is activated by the enzyme 25-hydroxylase in the liver to mediate its effects in the body, or most importantly, the kidneys and bones. The pharmacological actions of alfacalcidol are prolonged than vitamin D because a negative feedback mechanism regulates the final activation step of vitamin D in the kidneys.
Alfacalcidol is available in oral and intravenous formulations. In Canada, it is marketed as ONE-ALPHA, which manages hypocalcemia, secondary hyperparathyroidism, and osteodystrophy in adults with chronic renal failure. In approving European countries, alfacalcidol is also indicated for managing nutritional and malabsorptive rickets and osteomalacia, vitamin D-dependent rickets and osteomalacia, and hypophosphataemic vitamin D resistant rickets and osteomalacia.
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| CAS Number: |
41294-56-8
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| Molecular Weight: |
400.6371
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| DrugBank Indication: |
Alfacalcidol is indicated in adult patients with chronic renal failure for the management of hypocalcemia, secondary hyperparathyroidism, or osteodystrophy.
Alfacalcidol is indicated in the management of nutritional and malabsorptive rickets and osteomalacia, vitamin D-dependent rickets and osteomalacia, and hypophosphataemic vitamin D resistant rickets and osteomalacia.
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| DrugBank Pharmacology: |
Alfacalcidol works to increase serum levels of calcium by stimulating intestinal calcium absorption, reabsorption of calcium from bone, and possibly the renal reabsorption of calcium. It also modestly promotes intestinal phosphorus absorption. In patients with renal failure, alfacalcidol increased intestinal calcium and phosphorus absorption in a dose-related manner. This increase in calcium and phosphorus levels occurs within three days following drug administration: this effect was reversed within three days of drug discontinuation. In patients with chronic renal failure, serum calcium levels were elevated while parathyroid hormone and alkaline phosphatase levels returned to normal levels within five days following alfacalcidol administration. Since alfacalcidol suppresses parathyroid hormone, a reduction in parathyroid hormone levels is achieved more rapidly in patients on intermittent intravenous therapy, with significant reductions occurring within three months of therapy. In patients receiving daily oral therapy of alfacalcidol, the time it takes alfacalcidol to normalize plasma calcium levels may be up to several months, possibly reflecting calcium being utilized for bone mineralization. In patients with nutritional osteomalacia, alfacalcidol increased calcium absorption with six hours of oral administration and the effects peaked at 24 hours.
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| DrugBank MoA: |
In conditions like chronic renal failure, renal bone disease, hypoparathyroidism, and vitamin D dependent rickets, the kidneys' capacity for 1α-hydroxylation is impaired, leading to reduced production of endogenous 1,25-dihydroxyvitamin D and aberrated mineral metabolism. As an active and potent analog of vitamin D, alfacalcidol works to restore the functions and activities of endogenous 1,25-dihydroxyvitamin D.
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| Targets: |
Vitamin D3 receptor agonist; 25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial; Retinoic acid receptor RXR-alpha
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| Inclusion Criteria: |
Indication associated
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