Description

Cholecalciferol, also known as VitaminD3​, is a fat-soluble vitamin. It is a secosteroid produced in the skin upon exposure to ultraviolet B (UVB) sunlight. It can also be obtained from dietary sources (e.g., fatty fish, fortified foods) or supplements. The 200,000 IU dosage is a very high-potency formulation, typically administered as a single dose or a limited number of doses, and is used for therapeutic rather than daily maintenance purposes.

Indication

The 200,000 IU dose of cholecalciferol is indicated for the treatment of severe vitamin D deficiency. This high-dose therapy is used to rapidly replenish the body’s vitamin D stores and is typically prescribed when:

• Severe Vitamin D Deficiency: Blood levels of 25-hydroxyvitamin D are critically low, often below 12 ng/mL (30 nmol/L).
• Rickets: In children, severe vitamin D deficiency can cause rickets, a condition leading to bone softening and skeletal deformities.

• Osteomalacia: In adults, severe deficiency can cause osteomalacia, which results in bone pain and muscle weakness.

• Malabsorption Syndromes: Patients with conditions that impair fat absorption (e.g., cystic fibrosis, celiac disease, bariatric surgery) often require high-dose therapy to correct their deficiency.

• Renal and Liver Failure: While other forms of vitamin D might be needed, high-dose cholecalciferol may be used in certain stages of these diseases to build up stores.

This high-dose regimen is not intended for long-term daily use and should be administered under medical supervision to avoid the risk of vitamin D toxicity.

Mechanism of Action

Cholecalciferol itself is biologically inert. Its mechanism of action relies on a two-step metabolic activation process that occurs in the body.

1. First Hydroxylation (in the Liver): After absorption, cholecalciferol is transported to the liver. There, an enzyme called 25-hydroxylase converts it into calcidiol (25-hydroxyvitaminD3​). This is the major circulating form of vitamin D, and its blood level is used as the primary indicator of a person’s vitamin D status. Calcidiol is also a storage form of the vitamin.
2. Second Hydroxylation (in the Kidneys): Calcidiol is then transported to the kidneys. A second enzyme, 1-alpha-hydroxylase, converts it into the biologically active hormonal form, calcitriol (1,25-dihydroxyvitaminD3​). This is the final, most potent form of vitamin D.
3. Hormonal Action of Calcitriol: Calcitriol acts by binding to the vitamin D receptor (VDR) in various cells, initiating a range of actions to regulate calcium and phosphate homeostasis:
   • Intestinal Absorption: Calcitriol is the primary hormone that promotes the absorption of dietary calcium and phosphate from the small intestine, which is crucial for maintaining proper blood levels.

• • Bone Metabolism: It works in concert with parathyroid hormone (PTH) to regulate bone remodeling, promoting bone mineralization and, when necessary, mobilizing calcium from bone to maintain blood calcium levels.

• • Renal Reabsorption: It increases the reabsorption of calcium and phosphate in the kidneys, conserving these minerals.

By providing a large dose of cholecalciferol, the body is given a substantial amount of substrate to convert into these active metabolites, thereby rapidly correcting the deficiency and restoring normal calcium and phosphate balance.