What is Calcitriol?
Calcitriol is the active hormonal form of vitamin D (1,25-dihydroxyvitamin D3), a synthetic pharmaceutical agent that directly regulates calcium absorption from the gastrointestinal tract and is primarily used to treat secondary hyperparathyroidism and bone disease in chronic kidney disease patients. 1
Chemical and Pharmacological Properties
Calcitriol is chemically designated as 1α,25-dihydroxycholecalciferol or 1,25(OH)2D3, a white crystalline compound with a molecular weight of 416.65 that is soluble in organic solvents but relatively insoluble in water 1
It is the most physiologically active metabolite of vitamin D, naturally synthesized in the kidneys through the action of 1α-hydroxylase (CYP27B1), which converts 25-hydroxyvitamin D into the active form 2
Calcitriol binds to the vitamin D receptor (VDR) to exert its biological effects, including stimulation of intestinal calcium and phosphate absorption, suppression of parathyroid hormone (PTH) synthesis, and regulation of bone metabolism 2
Mechanism of Action and Physiological Role
Calcitriol functions as a hormone rather than a nutritional supplement, distinguishing it fundamentally from cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2) 3, 4
At the bone level, calcitriol suppresses pre-osteoblasts and activates mature osteoblasts, while also regulating immune response, cell differentiation, renin production, and reducing proteinuria 2
The compound has the most potent hypercalcemic effect among all vitamin D compounds in both normal subjects and patients with renal failure 5
Clinical Formulations
Calcitriol is available as oral capsules containing 0.25 mcg or 0.5 mcg, and as an oral solution containing 1 mcg/mL 1
All formulations contain butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) as antioxidants, with capsules containing fractionated triglyceride of coconut oil and oral solution containing fractionated triglyceride of palm seed oil 1
Critical Distinction from Nutritional Vitamin D
Calcitriol should never be used to treat nutritional vitamin D deficiency or insufficiency, as it does not raise 25-hydroxyvitamin D levels and serves an entirely different therapeutic purpose 4
Nutritional vitamin D deficiency must be corrected with ergocalciferol or cholecalciferol before prescribing calcitriol, as these represent separate clinical issues requiring different treatments 4
Unlike its precursors, calcitriol bypasses both hepatic 25-hydroxylation and renal 1α-hydroxylation, making it immediately active but also requiring no metabolic conversion 5
Primary Therapeutic Applications
The primary indication for calcitriol is treatment of secondary hyperparathyroidism in chronic kidney disease (CKD) stages 3-5, where endogenous calcitriol production is impaired 3, 2
In CKD patients, calcitriol is used to reverse high-turnover bone disease (osteitis fibrosa) and treat defective mineralization when PTH levels exceed specific thresholds 3
Additional therapeutic uses include prevention of bone loss in kidney transplant patients and reduction of proteinuria in IgA nephropathy 2