Hidroferol

Indications

• Vitamin D deficiency
• Rickets
• Osteomalacia

Mechanism of action

Calcifediol is transformed in the kidney by 25-hydroxyvitamin D3-1-(alpha)-hydroxylase to calcitriol, the active form of vitamin D3. Calcitriol binds to intracellular vitamin D receptors (VDR) that function as transcription factors to modulate gene expression. The VDR forms a heterodimer with the retinoid-X receptor, which binds to DNA, typically activating transcription of genes involved in calcium and phosphorus homeostasis. Calcitriol increases serum calcium concentrations by enhancing gastrointestinal absorption of calcium and phosphorus, promoting osteoclastic resorption, and increasing renal tubular reabsorption of calcium.

Pharmacodynamics

Calcifediol is essential for regulating calcium and phosphorus levels in the body, crucial for bone mineralization. Deficiency in vitamin D leads to rickets in children and osteomalacia in adults, conditions associated with impaired bone matrix mineralization. The pharmacodynamic effects of calcifediol include increased intestinal absorption of calcium, enhanced renal reabsorption of calcium, and increased mobilization of calcium and phosphorus from bone, which collectively help maintain skeletal integrity and metabolic functions.

Pharmacokinetics

Calcifediol is absorbed in the gastrointestinal tract and is primarily metabolized in the liver to 25-hydroxyvitamin D3. Its half-life is approximately two to three weeks, allowing for significant storage in body fat. The renal conversion to calcitriol is tightly regulated by serum levels of calcium and phosphorus, as well as parathyroid hormone (PTH) levels, ensuring that calcium homeostasis is maintained. Calcifediol is excreted primarily in bile and can also be eliminated via the kidneys.

Adverse effects

• Hypercalcemia
• Hyperphosphatemia
• Nausea
• Vomiting
• Constipation
• Weakness
• Headache

Precautions

• Monitor serum calcium levels during treatment.
• Use with caution in patients with kidney disease or hypercalcemia.

Pregnancy

Calcifediol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Calcifediol is excreted in breast milk; caution should be exercised when administered to nursing mothers.

Storage

Store in a cool, dry place away from light.

Formulations

• Oral solution
• Tablets

Mechanism of action

Calcidiol is transformed in the kidney by 25-hydroxyvitamin D3-1-(alpha)-hydroxylase to calcitriol, the active form of vitamin D3. Calcitriol binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Calcitriol increases the serum calcium concentrations by: increasing GI absorption of phosphorus and calcium, increasing osteoclastic resorption, and increasing distal renal tubular reabsorption of calcium. Calcitriol appears to promote intestinal absorption of calcium through binding to the vitamin D receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein.

Pharmacodynamics

Calcidiol is the precursor of vitamin D3. Vitamin D3 is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, in mineralization of bone, and for the assimilation of vitamin A. The classical manifestations of vitamin D deficiency is rickets, which is seen in children and results in bony deformaties including bowed long bones. Deficiency in adults leads to the disease osteomalacia. Both rickets and osteomalacia reflect impaired mineralization of newly synthesized bone matrix, and usually result from a combination of inadequate exposure to sunlight and decreased dietary intake of vitamin D. Common causes of vitamin D deficiency include genetic defects in the vitamin D receptor, severe liver or kidney disease, and insufficient exposure to sunlight. Vitamin D plays an important role in maintaining calcium balance and in the regulation of parathyroid hormone (PTH). It promotes renal reabsorption of calcium, increases intestinal absorption of calcium and phosphorus, and increases calcium and phosphorus mobilization from bone to plasma.