ALFACALCIDOL

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H44O2
Molecular Weight	400.6371
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)CCC[C@@H](C)[C@H]1CC[C@@H]2[C@]1(C)CCC\C2=C/C=C3/C[C@@H](O)C[C@H](O)C3=C

InChI

InChIKey=OFHCOWSQAMBJIW-AVJTYSNKSA-N

InChI=1S/C27H44O2/c1-18(2)8-6-9-19(3)24-13-14-25-21(10-7-15-27(24,25)5)11-12-22-16-23(28)17-26(29)20(22)4/h11-12,18-19,23-26,28-29H,4,6-10,13-17H2,1-3,5H3/b21-11+,22-12-/t19-,23-,24-,25+,26+,27-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C27H44O2
Molecular Weight	400.6371
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	6 / 6
E/Z Centers	2
Optical Activity	UNSPECIFIED

Description
Sources: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con135016.pdf
Curator's Comment: Description was created based on several sources, including http://www.sciencedirect.com/science/article/pii/B9780080552323611845 | https://www.ncbi.nlm.nih.gov/pubmed/19924035

Alfacalcidol (1-hydroxyvitamin D3) is a synthetic analog of vitamin D introduced clinically in the early 1970s. A prodrug for calcitriol (1,25-dihydroxyvitamin D3), it is one of the most potent and rapidly acting compounds currently used in the prevention and treatment of vitamin D deficiency states and hypocalcemia. The clinical benefit of alfacalcidol is related to the stimulation of calcium and phosphorus absorption, reversal of myopathy, promotion of mineralization in bone and the ability to reabsorb fully mineralized bone. Similar marketed vitamin D compounds include calcitriol and ergocalciferol. Alfacalcidol is indicated in conditions where there is a disturbance of calcium metabolism due to impaired 1-α hydroxylation such as when there is reduced renal function.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Vitamin D receptor 25 Target ID: CHEMBL1977 Sources: https://www.drugbank.ca/drugs/DB01436#targets \| http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con135016.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/19924035	Agonist 2752

Conditions

Condition	Modality	Highest Phase	Product
Renal osteodystrophy 11 Sources: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con135016.pdf	Primary	Approved 8583	Alfacalcidol Approved Use Alfacalcidol is indicated in conditions where there is a disturbance of calcium metabolism due to impaired 1-α hydroxylation such as when there is reduced renal function. The main indications are: a) Renal osteodystrophy b) Hyperparathyroidism (with bone disease) c) Hypoparathyroidism d) Neonatal hypocalcaemia e) Nutritional and malabsorptive rickets and osteomalacia f) Pseudo-deficiency (D-dependent) rickets and osteomalacia g) Hypophosphataemic vitamin D resistant rickets and osteomalacia
Hyperparathyroidism 1 Sources: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con135016.pdf	Primary	Approved 8583	Alfacalcidol Approved Use Alfacalcidol is indicated in conditions where there is a disturbance of calcium metabolism due to impaired 1-α hydroxylation such as when there is reduced renal function. The main indications are: a) Renal osteodystrophy b) Hyperparathyroidism (with bone disease) c) Hypoparathyroidism d) Neonatal hypocalcaemia e) Nutritional and malabsorptive rickets and osteomalacia f) Pseudo-deficiency (D-dependent) rickets and osteomalacia g) Hypophosphataemic vitamin D resistant rickets and osteomalacia
Hypoparathyroidism 5 Sources: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con135016.pdf	Primary	Approved 8583	Alfacalcidol Approved Use Alfacalcidol is indicated in conditions where there is a disturbance of calcium metabolism due to impaired 1-α hydroxylation such as when there is reduced renal function. The main indications are: a) Renal osteodystrophy b) Hyperparathyroidism (with bone disease) c) Hypoparathyroidism d) Neonatal hypocalcaemia e) Nutritional and malabsorptive rickets and osteomalacia f) Pseudo-deficiency (D-dependent) rickets and osteomalacia g) Hypophosphataemic vitamin D resistant rickets and osteomalacia
Rickets 3 Sources: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con135016.pdf	Primary	Approved 8583	Alfacalcidol Approved Use Alfacalcidol is indicated in conditions where there is a disturbance of calcium metabolism due to impaired 1-α hydroxylation such as when there is reduced renal function. The main indications are: a) Renal osteodystrophy b) Hyperparathyroidism (with bone disease) c) Hypoparathyroidism d) Neonatal hypocalcaemia e) Nutritional and malabsorptive rickets and osteomalacia f) Pseudo-deficiency (D-dependent) rickets and osteomalacia g) Hypophosphataemic vitamin D resistant rickets and osteomalacia
Osteomalacia 2 Sources: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con135016.pdf	Primary	Approved 8583	Alfacalcidol Approved Use Alfacalcidol is indicated in conditions where there is a disturbance of calcium metabolism due to impaired 1-α hydroxylation such as when there is reduced renal function. The main indications are: a) Renal osteodystrophy b) Hyperparathyroidism (with bone disease) c) Hypoparathyroidism d) Neonatal hypocalcaemia e) Nutritional and malabsorptive rickets and osteomalacia f) Pseudo-deficiency (D-dependent) rickets and osteomalacia g) Hypophosphataemic vitamin D resistant rickets and osteomalacia

C_max

Value	Dose	Analyte	Population
67.492 pg/mL OTHER GOV'T https://mhraproducts4853.blob.core.windows.net/docs/5b74a841dd7fdbfa216d1071546233c80df37bd3#page=9	1 μg single, oral dose: 1 μg route of administration: Oral experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
57.49 pg/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400061_3112001M1259_1_902_1F.pdf#page=20	4 μg single, oral dose: 4 μg route of administration: Oral experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
76.96 pg/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400061_3112001M1259_1_902_1F.pdf#page=21	3 μg single, oral dose: 3 μg route of administration: Oral experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
63.4 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11981071/	4 μg single, intravenous dose: 4 μg route of administration: Intravenous experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
70.9 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11981071/	4 μg single, oral dose: 4 μg route of administration: Oral experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
147 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11981071/	4 μg single, intravenous dose: 4 μg route of administration: Intravenous experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
73 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11981071/	4 μg single, oral dose: 4 μg route of administration: Oral experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
3296.928 pg × h/mL OTHER GOV'T https://mhraproducts4853.blob.core.windows.net/docs/5b74a841dd7fdbfa216d1071546233c80df37bd3#page=9	1 μg single, oral dose: 1 μg route of administration: Oral experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2305 pg × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400061_3112001M1259_1_902_1F.pdf#page=20	4 μg single, oral dose: 4 μg route of administration: Oral experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
3837.179 pg × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400061_3112001M1259_1_902_1F.pdf#page=21	3 μg single, oral dose: 3 μg route of administration: Oral experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1365.6 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11981071/	4 μg single, intravenous dose: 4 μg route of administration: Intravenous experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
1074.1 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11981071/	4 μg single, oral dose: 4 μg route of administration: Oral experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
2957.9 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11981071/	4 μg single, intravenous dose: 4 μg route of administration: Intravenous experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2092.1 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11981071/	4 μg single, oral dose: 4 μg route of administration: Oral experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
20.92 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400061_3112001M1259_1_902_1F.pdf#page=20	4 μg single, oral dose: 4 μg route of administration: Oral experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
14.275 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/400061_3112001M1259_1_902_1F.pdf#page=21	3 μg single, oral dose: 3 μg route of administration: Oral experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
48.63 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11981071/	4 μg single, intravenous dose: 4 μg route of administration: Intravenous experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
47.13 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11981071/	4 μg single, oral dose: 4 μg route of administration: Oral experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
36.66 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11981071/	4 μg single, intravenous dose: 4 μg route of administration: Intravenous experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
29.19 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11981071/	4 μg single, oral dose: 4 μg route of administration: Oral experiment type: SINGLE co-administered:	CALCITRIOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
19% EXPERIMENT https://www.jstage.jst.go.jp/article/vso/52/9-10/52_KJ00001705074/_article/-char/en			ALFACALCIDOL plasma	Homo sapiens

Doses

Dose	Population	Adverse events
2 ug 1 times / day multiple, oral Highest studied dose Dose: 2 ug, 1 times / day Route: oral Route: multiple Dose: 2 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/33339609/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/33339609/	Sources: https://pubmed.ncbi.nlm.nih.gov/33339609/
3 ug 1 times / week multiple, intravenous Highest studied dose Dose: 3 ug, 1 times / week Route: intravenous Route: multiple Dose: 3 ug, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21401359/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21401359/	Sources: https://pubmed.ncbi.nlm.nih.gov/21401359/
1 ug 1 times / day multiple, oral Recommended Dose: 1 ug, 1 times / day Route: oral Route: multiple Dose: 1 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30461612/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30461612/	Disc. AE: Hypercalciuria, Ureteral calculus... AEs leading to discontinuation/dose reduction: Hypercalciuria (27%) Ureteral calculus (1.6%) Hydronephrosis (1.6%) Stomach ache (1.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/30461612/

AEs

AE	Significance	Dose	Population
Hydronephrosis	1.6% Disc. AE	1 ug 1 times / day multiple, oral Recommended Dose: 1 ug, 1 times / day Route: oral Route: multiple Dose: 1 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30461612/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30461612/
Stomach ache	1.6% Disc. AE	1 ug 1 times / day multiple, oral Recommended Dose: 1 ug, 1 times / day Route: oral Route: multiple Dose: 1 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30461612/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30461612/
Ureteral calculus	1.6% Disc. AE	1 ug 1 times / day multiple, oral Recommended Dose: 1 ug, 1 times / day Route: oral Route: multiple Dose: 1 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30461612/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30461612/
Hypercalciuria	27% Disc. AE	1 ug 1 times / day multiple, oral Recommended Dose: 1 ug, 1 times / day Route: oral Route: multiple Dose: 1 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30461612/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30461612/

PubMed

Title	Date	PubMed
Active vitamin D and acute respiratory infections in dialysis patients.	2011-06	21617088
Synergistic effects of green tea polyphenols and alphacalcidol on chronic inflammation-induced bone loss in female rats.	2010-11	20069278
Hydrogen/deuterium exchange reveals distinct agonist/partial agonist receptor dynamics within vitamin D receptor/retinoid X receptor heterodimer.	2010-10-13	20947021
Autosomal dominant hypocalcemia caused by an activating mutation of the calcium-sensing receptor gene: the first case report in Korea.	2010-02	20119591
Calcium-alkali syndrome-like symptoms manifested by daily alphacalcidol and thiazide.	2010	20453404
Modulation of bile acid metabolism by 1alpha-hydroxyvitamin D3 administration in mice.	2009-10	19581390
Metabolism of 1alpha-hydroxyvitamin D3 by cytochrome P450scc to biologically active 1alpha,20-dihydroxyvitamin D3.	2008-12	19000766
A case of X-linked hypophosphatemic rickets: complications and the therapeutic use of cinacalcet.	2008-12	18775977
Lithocholic acid derivatives act as selective vitamin D receptor modulators without inducing hypercalcemia.	2008-04	18180267
Functional evolution of the vitamin D and pregnane X receptors.	2007-11-12	17997857
Chemopreventive effect of a vitamin D(3) analog, alfacalcidol, on colorectal carcinogenesis in mice with ulcerative colitis.	2007-11	17893519
Hereditary vitamin D-resistant rickets in Greek children: genotype, phenotype, and long-term response to treatment.	2007-03	17451081
The vitamin D prodrugs 1alpha(OH)D2, 1alpha(OH)D3 and BCI-210 suppress PTH secretion by bovine parathyroid cells.	2006-03	16221703
1-alpha-calcidol modulates major human monocyte antigens and toll-like receptors TLR 2 and TLR4 in vitro.	2005-04-20	15946915
CYP3A4 is a human microsomal vitamin D 25-hydroxylase.	2004-04	15005856
Supplementation with Alfacalcidol increases protein intake and serum albumin concentration in patients undergoing hemodialysis with hpoalbumineamia.	2004	15044820
Vascular influences of calcium supplementation and vitamin D-induced hypercalcemia in NaCl-hypertensive rats.	2003-09	12960676
Kidney microsomal 25- and 1alpha-hydroxylase in vitamin D metabolism: catalytic properties, molecular cloning, cellular localization and expression during development.	2002-02-28	11880238
Alfacalcidol in the therapy of renal bone disease.	2001-12	11770836
Activating mutations of the calcium-sensing receptor: management of hypocalcemia.	2001-11	11701698
Chronotherapy with active vitamin D3 in aged stroke-prone spontaneously hypertensive rats, a model of osteoporosis.	2001-10-05	11675047
Association of transforming growth factor beta1 genotype with therapeutic response to active vitamin D for postmenopausal osteoporosis.	2000-03	10750555
Effect of 1 alpha-hydroxyvitamin D3 on serum levels of thyroid hormones in hyperthyroid patients with untreated Graves' disease.	1997-10	9322804
Effect of 22-oxacalcitriol on hyperparathyroidism of dialysis patients: results of a preliminary study.	1996	8840326
Increase of renal 25-hydroxyvitamin D3-24-hydroxylase activity and its messenger ribonucleic acid level in 1 alpha-hydroxyvitamin D3-administered rats: possibility of the presence of two forms of 24-hydroxylase.	1993-04	8410379
[Vitamin D-resistant rickets type II: apropos of 2 cases].	1992	1338926
Transformation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3 by using Streptomyces sp. strains.	1991-10	1746944
Danazol-induced hypercalcaemia in alphacalcidol-treated hypoparathyroidism.	1989-11	2616424
Possible role for vitamin D in controlling breast cancer cell proliferation.	1989-01-28	2563099
1 alpha-hydroxyvitamin D3 treatment of three patients with 1,25-dihydroxyvitamin D-receptor-defect rickets and alopecia.	1987-07	3037475
Alfacalcidol as a modulator of growth of low grade non-Hodgkin's lymphomas.	1985-10-26	2996693
Aspirin inhibition of 1 alpha-hydroxyvitamin D3 or parathyroid hormone induced hypercalcemia in vivo in rats. A mechanism independent of prostaglandin biosynthesis inhibition.	1985-06-01	4004906
[Transient vitamin-D dependent rickets? a case report differential diagnosis (author's transl)].	1982	6285251

Patents

Sample Use Guides

In Vivo Use Guide

Initial dose for all indications: Adults: 1 microgram/day Dosage in the elderly: 0.5 microgram/day Neonates and premature infants: 0.05 – 0.1 microgram/kg/day Children under 20kg bodyweight: 0.05 microgram/kg/day Children over 20kg bodyweight: 1 microgram/day

Route of Administration: Oral

In Vitro Use Guide

Preincubation of aortic rings with alfacalcidol 10 uM significantly inhibited phenylephrine-induced contractions

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:08:37 GMT 2025` Edited by `admin` on `Mon Mar 31 18:08:37 GMT 2025`
Record UNII	URQ2517572
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

1.ALPHA.-HYDROXYCHOLECALCIFEROL

Preferred Name

English

ALFACALCIDOL

Official Name

English

1.ALPHA.-HYDROXYCHOLECALCIFEROL [MI]

Common Name

English

1-HYDROXYVITAMIN D3

Common Name

English

ETALPHA

Brand Name

English

1.ALPHA.-HYDROXYVITAMIN D3

Common Name

English

1-ALPHA-VITAMIN D

Common Name

English

1.ALPHA.(OH)D3

Common Name

English

1-HYDROXYCHOLECALCIFEROL

Common Name

English

(5Z,7E)-9,10-SECOCHOLESTA-5,7,10(19)-TRIENE-1.ALPHA.,3.BETA.-DIOL

Common Name

English

UN ALFA

Brand Name

English

1.ALPHA-HYDROXYCHOLECALCIFEROL

Common Name

English

UN ALPHA

Brand Name

English

ALFACALCIDOL [MART.]

Common Name

English

BONDIOL

Brand Name

English

ALFACALCIDOL [JAN]

Common Name

English

1,3-CYCLOHEXANEDIOL, 5-((2E)-2-((1R,3AS,7AR)-1-((1R)-1,5-DIMETHYLHEXYL)OCTAHYDRO-7A-METHYL-4H-INDEN-4-YLIDENE)ETHYLIDENE)-4-METHYLENE-, (1R,3R)-

Common Name

English

ALPHA D3

Brand Name

English

ALPHAROL

Brand Name

English

ALSIODOL

Brand Name

English

TEVABONE

Common Name

English

ALFACALCIDOL [EP MONOGRAPH]

Common Name

English

EINSALPHA

Brand Name

English

ALFAROL

Brand Name

English

OXYDEVIT

Brand Name

English

.ALPHA.-CALCIDOL

Common Name

English

alfacalcidol [INN]

Common Name

English

ALPHACALCIDOL

Brand Name

English

Alfacalcidol [WHO-DD]

Common Name

English

9,10-SECOCHOLESTA-5,7,10(19)-TRIENE-1,3-DIOL, (1.ALPHA.,3.BETA.,5Z,7E)-

Common Name

English

Classification Tree Code System Code

WHO-ATC

M05BB06