125dihydroxycholecalciferol

1,25-dihydroxycholecalciferol, commonly known as calcitriol, is the hormonally active metabolite of vitamin D3. It is produced in the kidney by the enzyme 1-alpha-hydroxylase from 25-hydroxycholecalciferol (calcidiol) in response to parathyroid hormone and signals related to low serum calcium. Calcitriol, together with its precursor, maintains calcium and phosphate homeostasis and promotes bone mineralization.

Calcitriol exerts its effects by binding to the vitamin D receptor (VDR) in the nucleus, forming a heterodimer with the retinoid X receptor and regulating transcription of genes involved in mineral handling. It increases intestinal absorption of calcium and phosphate by upregulating transport proteins such as TRPV6 and calbindin. It also influences bone remodeling, in part by stimulating RANKL expression on osteoblasts, which promotes osteoclast activity and facilitates mineral exchange within bone.

Regulation of renal calcitriol synthesis is tightly controlled by parathyroid hormone, serum calcium and phosphate levels, and fibroblast growth factor 23. Calcitriol catabolism is increased by 24-hydroxylase (CYP24A1), producing inactive metabolites. FGF23 inhibits 1-alpha-hydroxylase and promotes 24-hydroxylase, forming a negative feedback loop that helps maintain mineral balance.

Clinical use of calcitriol includes treatment of hypocalcemia in chronic kidney disease and hypoparathyroidism, as well as vitamin D deficiency where rapid correction is desired. It is also used topically for certain dermatologic conditions in some settings. Adverse effects include hypercalcemia and hypercalciuria; contraindications include hypercalcemia, nephrolithiasis risk, or conditions of vitamin D toxicity. Calcitriol has a relatively short half-life and is metabolized in the liver, with excretion of metabolites via bile and urine.