Calcitriol
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| Pronunciation | US: /ˌkælsɪˈtraɪɒl/;[1][2][3][4][5] UK: /kælˈsɪtriɒl/ |
| Trade names | Rocaltrol, Calcijex, Decostriol, others |
| Other names | 1,25-dihydroxycholecalciferol, 1alpha,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D3, 1α,25-(OH)2D3, 1,25(OH)2D[6] |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682335 |
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intravenous[7] | |
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| Protein binding | 99.9% |
| Metabolism | Kidney |
| Elimination half-life | 5–8 hours (adults), 27 hours (children) |
| Excretion | Faeces (50%), urine (16%) |
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Calcitriol is the active form of
It can be given as a medication for the treatment of
Calcitriol was identified as the active form of vitamin D in 1971 and the drug was approved for medical use in the United States in 1978.
Medical use
Calcitriol is prescribed for:[16]
- Treatment of hypocalcaemia – hypoparathyroidism, osteomalacia (adults), rickets (infants, children), renal osteodystrophy, chronic kidney disease
- Treatment of osteoporosis
- Prevention of corticosteroid-induced osteoporosis
Calcitriol has been used in an ointment for the treatment of
Adverse effects
The main
High calcitriol levels may also be seen in human disease states in patients not on supplementation. In someone with hypercalcaemia and high calcitriol levels, low intact parathyroid hormone levels are usually present.
The major conditions with hypercalcaemia due to elevated calcitriol levels are
- Fungal infections; Pneumocystis jiroveci, histoplasmosis, coccidioidomycosis, paracoccidioidomycosis, candidiasis
- Other granulomatous conditions; PR3+ vasculitis, Crohn's disease, acute granulomatous pneumonia, talc granuloma, silicone-induced granuloma, BCG-associated, granulomatous hepatitis, paraffin-associated granuloma
- Genetic conditions; Williams syndrome, pseudoxanthoma elasticum, CYP24A1 mutation (adult / infantile), SLC34A1 mutation
- Miscellaneous; mycobacterium avium, leprosy, lipoid pneumonia, cat scratch fever, berylliosis
Some plants contain glycosides of
Mechanism of action
Calcitriol increases blood calcium levels ([Ca2+
]) by:
- Promoting absorption of dietary calcium from the gastrointestinal tract.
- Increasing renal tubularreabsorption of calcium, thus reducing the loss of calcium in the urine.
- Stimulating release of calcium from bone. For this it acts on the specific type of bone cells referred to as osteoclasts.[24]
Calcitriol acts in concert with
. The resulting decrease in serum phosphate causes hydroxyapatite (Ca5(PO4)3OH) to dissolve out of bone, thus increasing serum calcium. PTH also stimulates the production of calcitriol (see below).[25]
Many of the effects of calcitriol are mediated by its interaction with the
The maintenance of electroneutrality requires that the transport of Ca2+
ions catalyzed by the intestinal epithelial cells be accompanied by counterions, primarily inorganic phosphate. Thus calcitriol also stimulates the intestinal absorption of phosphate.[25]
The observation that calcitriol stimulates the release of calcium from bone seems contradictory, given that sufficient levels of serum calcitriol generally prevent overall loss of calcium from bone. It is believed that the increased levels of serum calcium resulting from calcitriol-stimulated intestinal uptake causes bone to take up more calcium than it loses by hormonal stimulation of osteoclasts.[25] Only when there are conditions, such as dietary calcium deficiency or defects in intestinal transport, which result in a reduction of serum calcium does an overall loss of calcium from bone occur.
Calcitriol also inhibits the release of calcitonin,[28] a hormone which reduces blood calcium primarily by inhibiting calcium release from bone.[25]
Biosynthesis and its regulation
Calcitriol is produced in the cells of the
The activity of this enzyme is stimulated by PTH. This is an important control point in
Calcitriol is also produced outside the kidney in small amounts by many other tissues including
When the drug alfacalcidol is used, 25-hydroxylation in the liver produces calcitriol as the active metabolite. This will produce greater effects than other vitamin D precursors in patients with kidney disease who have loss of the renal 1-alpha-hydroxylase.[32]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
- ^ The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".
Metabolism
The halflife of calcitriol in the body is measured in hours, unlike its precursor calcifediol, whose halflife is measured in weeks.[33] Calcitriol is inactivated by further hydroxylation to form 1,24,25-trihydroxyvitamin D, calcitroic acid. This occurs through the action of the CYP24A1 24-hydroxylase.[34] Calcitroic acid is more soluble in water and is excreted in bile and urine.
History
It was first identified in 1971 by Michael F. Holick working in the laboratory of Hector DeLuca,[35][36] and also by Tony Norman and colleagues.[37]
Names
Calcitriol refers specifically to 1,25-dihydroxycholecalciferol. Because cholecalciferol already has one hydroxyl group, only two (1,25) are further specified in this nomenclature, but in fact there are three (1,3,25-triol), as indicated by the name calcitriol. The 1-hydroxy group is in the alpha position, and this may be specified in the name, for instance in the abbreviation 1α,25-(OH)2D3.[6]
Calcitriol is, strictly, the 1-hydroxylation product of calcifediol (25-OH vitamin D3), derived from cholecalciferol (vitamin D3), rather than the product of hydroxylations of ergocalciferol (vitamin D2).[6] 1α,25-Dihydroxyergocalciferol (ercalcitriol) should be used for the vitamin D2 product.[6] However, the terminology of 1,25-dihydroxyvitamin D, or 1,25(OH)2D, is often used to refer to both types of active forms of vitamin D. Indeed, both bind to the vitamin D receptor and produce biological effects.[38] In clinical use, the differences are unlikely to have major importance.[32]
Calcitriol is marketed as a pharmaceutical for medical use under various trade names including Rocaltrol (
References
- ^ Elsevier, Dorland's Illustrated Medical Dictionary, Elsevier.
- ^ Wolters Kluwer, Stedman's Medical Dictionary, Wolters Kluwer.
- ^ Merriam-Webster, Merriam-Webster's Medical Dictionary, Merriam-Webster.
- ^ Houghton Mifflin Harcourt, The American Heritage Dictionary of the English Language, Houghton Mifflin Harcourt, archived from the original on 25 September 2015, retrieved 25 September 2015.
- ^ Merriam-Webster, Merriam-Webster's Unabridged Dictionary, Merriam-Webster, archived from the original on 25 May 2020, retrieved 25 September 2015.
- ^ PMID 7094913.
- ^ a b c d e f g "Calcitriol Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 9 April 2019.
- S2CID 8894111.
- ISBN 9780128122006.
- ^ "Office of Dietary Supplements - Vitamin D". ods.od.nih.gov. 9 October 2020. Retrieved 31 October 2020.
- PMID 18689389.
- ^ ISBN 9780857113382.
- ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
- ^ "Calcitriol - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
- hdl:10665/345533. WHO/MHP/HPS/EML/2021.02. Archived(PDF) from the original on 23 January 2024.
- ^ ISBN 978-0-9757919-2-9.
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- ^ "Calcinogenic Glycosides". Plants Poisonous to Livestock. Cornell Department of Animal Science. Retrieved 16 June 2021.
- ISBN 978-0-07-159991-7.
- ^ ISBN 978-0-471-25090-6.
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