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Details

Stereochemistry ABSOLUTE
Molecular Formula C27H44O2
Molecular Weight 400.6371
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 2
Charge 0

SHOW SMILES / InChI
Structure of 25-HYDROXYCHOLECALCIFEROL, 5-TRANS-

SMILES

[H][C@@]1(CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C3/C[C@@H](O)CCC3=C)[C@H](C)CCCC(C)(C)O

InChI

InChIKey=JWUBBDSIWDLEOM-WIFPIRAHSA-N
InChI=1S/C27H44O2/c1-19-10-13-23(28)18-22(19)12-11-21-9-7-17-27(5)24(14-15-25(21)27)20(2)8-6-16-26(3,4)29/h11-12,20,23-25,28-29H,1,6-10,13-18H2,2-5H3/b21-11+,22-12+/t20-,23+,24-,25+,27-/m1/s1

HIDE SMILES / InChI

Molecular Formula C27H44O2
Molecular Weight 400.6371
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 2
Optical Activity UNSPECIFIED

Calcifediol (25-Hydroxyvitamin D3 or 25-hydroxycholecalciferol) is a biologically active vitamin D3 metabolite. It is concluded that the liver is the major if not the only physiologic site of hydroxylation of vitamin D3 into calcifediol. Calcifediol is a prohormone of the active form of vitamin D3, calcitriol (1,25-dihydroxyvitamin D3). Calcifediol is converted to calcitriol by cytochrome P450 27B1 (CYP27B1), also called 1-alpha hydroxylase, primarily in the kidney. Calcitriol binds to the vitamin D receptor in target tissues and activates vitamin D responsive pathways that result in increased intestinal absorption of calcium and phosphorus and reduced parathyroid hormone synthesis. RAYALDEE (calcifediol) extended-release capsules is indicated for the treatment of secondary hyperparathyroidism in adult patients with stage 3 or 4 chronic kidney disease.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
RAYALDEE

Approved Use

Calcifediol indicated for the treatment of secondary hyperparathyroidism in adults with stage 3 or 4 chronic kidney disease and serum total 25-hydroxyvitamin D levels less than 30 ng/mL

Launch Date

2016
Primary
CALDEROL

Approved Use

Unknown

Launch Date

1980
Primary
CALDEROL

Approved Use

Unknown

Launch Date

1980
Primary
CALDEROL

Approved Use

Unknown

Launch Date

1980
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
73.2 ng/mL
20 mg 1 times / day steady-state, oral
dose: 20 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CALCIFEDIOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1704.4 ng × h/mL
20 mg 1 times / day steady-state, oral
dose: 20 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CALCIFEDIOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
11 day
20 mg 1 times / day steady-state, oral
dose: 20 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CALCIFEDIOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
20 mg 1 times / day steady-state, oral
dose: 20 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CALCIFEDIOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
30 ug 1 times / day multiple, oral (starting)
Dose: 30 ug, 1 times / day
Route: oral
Route: multiple
Dose: 30 ug, 1 times / day
Sources:
unhealthy, 66 years (range: 25-85 years)
n = 285
Health Status: unhealthy
Condition: secondary hyperparathyroidism
Age Group: 66 years (range: 25-85 years)
Sex: M+F
Population Size: 285
Sources:
Other AEs: Anemia, Nasopharyngitis...
Other AEs:
Anemia (4.9%)
Nasopharyngitis (4.9%)
Blood creatinine increased (4.9%)
Dyspnea (4.2%)
Cough (3.5%)
Cardiac failure congestive (3.5%)
Constipation (3.2%)
Bronchitis (2.8%)
Hyperkalemia (2.5%)
Osteoarthritis (2.1%)
Hyperuricemia (1.8%)
Contusion (1.8%)
Pneumonia (1.4%)
Chronic obstructive pulmonary disease (1.4%)
Calcium increased serum (4.2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Chronic obstructive pulmonary disease 1.4%
30 ug 1 times / day multiple, oral (starting)
Dose: 30 ug, 1 times / day
Route: oral
Route: multiple
Dose: 30 ug, 1 times / day
Sources:
unhealthy, 66 years (range: 25-85 years)
n = 285
Health Status: unhealthy
Condition: secondary hyperparathyroidism
Age Group: 66 years (range: 25-85 years)
Sex: M+F
Population Size: 285
Sources:
Pneumonia 1.4%
30 ug 1 times / day multiple, oral (starting)
Dose: 30 ug, 1 times / day
Route: oral
Route: multiple
Dose: 30 ug, 1 times / day
Sources:
unhealthy, 66 years (range: 25-85 years)
n = 285
Health Status: unhealthy
Condition: secondary hyperparathyroidism
Age Group: 66 years (range: 25-85 years)
Sex: M+F
Population Size: 285
Sources:
Contusion 1.8%
30 ug 1 times / day multiple, oral (starting)
Dose: 30 ug, 1 times / day
Route: oral
Route: multiple
Dose: 30 ug, 1 times / day
Sources:
unhealthy, 66 years (range: 25-85 years)
n = 285
Health Status: unhealthy
Condition: secondary hyperparathyroidism
Age Group: 66 years (range: 25-85 years)
Sex: M+F
Population Size: 285
Sources:
Hyperuricemia 1.8%
30 ug 1 times / day multiple, oral (starting)
Dose: 30 ug, 1 times / day
Route: oral
Route: multiple
Dose: 30 ug, 1 times / day
Sources:
unhealthy, 66 years (range: 25-85 years)
n = 285
Health Status: unhealthy
Condition: secondary hyperparathyroidism
Age Group: 66 years (range: 25-85 years)
Sex: M+F
Population Size: 285
Sources:
Osteoarthritis 2.1%
30 ug 1 times / day multiple, oral (starting)
Dose: 30 ug, 1 times / day
Route: oral
Route: multiple
Dose: 30 ug, 1 times / day
Sources:
unhealthy, 66 years (range: 25-85 years)
n = 285
Health Status: unhealthy
Condition: secondary hyperparathyroidism
Age Group: 66 years (range: 25-85 years)
Sex: M+F
Population Size: 285
Sources:
Hyperkalemia 2.5%
30 ug 1 times / day multiple, oral (starting)
Dose: 30 ug, 1 times / day
Route: oral
Route: multiple
Dose: 30 ug, 1 times / day
Sources:
unhealthy, 66 years (range: 25-85 years)
n = 285
Health Status: unhealthy
Condition: secondary hyperparathyroidism
Age Group: 66 years (range: 25-85 years)
Sex: M+F
Population Size: 285
Sources:
Bronchitis 2.8%
30 ug 1 times / day multiple, oral (starting)
Dose: 30 ug, 1 times / day
Route: oral
Route: multiple
Dose: 30 ug, 1 times / day
Sources:
unhealthy, 66 years (range: 25-85 years)
n = 285
Health Status: unhealthy
Condition: secondary hyperparathyroidism
Age Group: 66 years (range: 25-85 years)
Sex: M+F
Population Size: 285
Sources:
Constipation 3.2%
30 ug 1 times / day multiple, oral (starting)
Dose: 30 ug, 1 times / day
Route: oral
Route: multiple
Dose: 30 ug, 1 times / day
Sources:
unhealthy, 66 years (range: 25-85 years)
n = 285
Health Status: unhealthy
Condition: secondary hyperparathyroidism
Age Group: 66 years (range: 25-85 years)
Sex: M+F
Population Size: 285
Sources:
Cardiac failure congestive 3.5%
30 ug 1 times / day multiple, oral (starting)
Dose: 30 ug, 1 times / day
Route: oral
Route: multiple
Dose: 30 ug, 1 times / day
Sources:
unhealthy, 66 years (range: 25-85 years)
n = 285
Health Status: unhealthy
Condition: secondary hyperparathyroidism
Age Group: 66 years (range: 25-85 years)
Sex: M+F
Population Size: 285
Sources:
Cough 3.5%
30 ug 1 times / day multiple, oral (starting)
Dose: 30 ug, 1 times / day
Route: oral
Route: multiple
Dose: 30 ug, 1 times / day
Sources:
unhealthy, 66 years (range: 25-85 years)
n = 285
Health Status: unhealthy
Condition: secondary hyperparathyroidism
Age Group: 66 years (range: 25-85 years)
Sex: M+F
Population Size: 285
Sources:
Calcium increased serum 4.2%
30 ug 1 times / day multiple, oral (starting)
Dose: 30 ug, 1 times / day
Route: oral
Route: multiple
Dose: 30 ug, 1 times / day
Sources:
unhealthy, 66 years (range: 25-85 years)
n = 285
Health Status: unhealthy
Condition: secondary hyperparathyroidism
Age Group: 66 years (range: 25-85 years)
Sex: M+F
Population Size: 285
Sources:
Dyspnea 4.2%
30 ug 1 times / day multiple, oral (starting)
Dose: 30 ug, 1 times / day
Route: oral
Route: multiple
Dose: 30 ug, 1 times / day
Sources:
unhealthy, 66 years (range: 25-85 years)
n = 285
Health Status: unhealthy
Condition: secondary hyperparathyroidism
Age Group: 66 years (range: 25-85 years)
Sex: M+F
Population Size: 285
Sources:
Anemia 4.9%
30 ug 1 times / day multiple, oral (starting)
Dose: 30 ug, 1 times / day
Route: oral
Route: multiple
Dose: 30 ug, 1 times / day
Sources:
unhealthy, 66 years (range: 25-85 years)
n = 285
Health Status: unhealthy
Condition: secondary hyperparathyroidism
Age Group: 66 years (range: 25-85 years)
Sex: M+F
Population Size: 285
Sources:
Blood creatinine increased 4.9%
30 ug 1 times / day multiple, oral (starting)
Dose: 30 ug, 1 times / day
Route: oral
Route: multiple
Dose: 30 ug, 1 times / day
Sources:
unhealthy, 66 years (range: 25-85 years)
n = 285
Health Status: unhealthy
Condition: secondary hyperparathyroidism
Age Group: 66 years (range: 25-85 years)
Sex: M+F
Population Size: 285
Sources:
Nasopharyngitis 4.9%
30 ug 1 times / day multiple, oral (starting)
Dose: 30 ug, 1 times / day
Route: oral
Route: multiple
Dose: 30 ug, 1 times / day
Sources:
unhealthy, 66 years (range: 25-85 years)
n = 285
Health Status: unhealthy
Condition: secondary hyperparathyroidism
Age Group: 66 years (range: 25-85 years)
Sex: M+F
Population Size: 285
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as victim
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Determination of vitamin D and its metabolites in plasma from normal and anephric man.
1979 Jul 15
Interrelationship of serum 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D in juvenile renal osteodystrophy after therapy with 25-hydroxyvitamin D3.
1982
Tubular aggregates in a case of osteomalacic myopathy due to anticonvulsant drugs.
1984 Jan-Feb
Hypercalcemia in 25 OH D3 treated patients receiving a calcium exchange resin.
1985 Jun
The effect of vitamin D status on cutaneous sterologenesis in vivo and in vitro.
1987 Sep 14
Inhibition of tubercle bacilli in cultured human macrophages by chloroquine used alone and in combination with streptomycin, isoniazid, pyrazinamide, and two metabolites of vitamin D3.
1990 Nov
1 alpha,25-dihydroxyvitamin D3 inhibits productive infection of human monocytes by HIV-1.
1991 Apr 30
Vitamin D3 compounds regulate human immunodeficiency virus type 1 replication in U937 monoblastoid cells and in monocyte-derived macrophages.
1993 Feb
Proteins in the heat shock-70 family specifically bind 25-hydroxyvitamin D3 and 17beta-estradiol.
1998 Apr
Calcidiol and PTH levels in women attending an osteoporosis program.
1999 Apr
A pilot study to assess the safety and efficacy of topical calcipotriol treatment in childhood psoriasis.
1999 Jul-Aug
Overview of general physiologic features and functions of vitamin D.
2004 Dec
Vitamin D(3) metabolism in human glioblastoma multiforme: functionality of CYP27B1 splice variants, metabolism of calcidiol, and effect of calcitriol.
2005 Aug 1
Vitamin D metabolism in human prostate cells: implications for prostate cancer chemoprevention by vitamin D.
2006 Jul-Aug
Functional evolution of the vitamin D and pregnane X receptors.
2007 Nov 12
Enhanced steatosis by nuclear receptor ligands: a study in cultured human hepatocytes and hepatoma cells with a characterized nuclear receptor expression profile.
2010 Mar 30
The evolution of farnesoid X, vitamin D, and pregnane X receptors: insights from the green-spotted pufferfish (Tetraodon nigriviridis) and other non-mammalian species.
2011 Feb 3
Patents

Sample Use Guides

The initial dose of RAYALDEE (calcifediol) extended-release capsules is 30 mcg administered orally once daily at bedtime. Serum calcium should be below 9.8 mg/dL before initiating treatment. Monitor serum calcium, phosphorus, 25-hydroxyvitamin D and intact parathyroid hormone (PTH) 3 months after starting therapy or changing dose. Increase the dose to 60 mcg once daily after 3 months if intact PTH is above the treatment goal. Ensure serum calcium is below 9.8 mg/dL, phosphorus is below 5.5 mg/dL and 25-hydroxyvitamin D is below 100 ng/mL before increasing the dose. Suspend dosing if intact PTH is persistently abnormally low, serum calcium is consistently above the normal range or serum 25­ hydroxyvitamin D is consistently above 100 ng/mL
Route of Administration: Oral
Vitamin D metabolites down-regulated stimulated IL-8 only in those hyperinflammatory monocyte-derived macrophages, and only when used at high doses (>100 nM for Calcifediol).
Substance Class Chemical
Created
by admin
on Sat Dec 16 01:53:38 GMT 2023
Edited
by admin
on Sat Dec 16 01:53:38 GMT 2023
Record UNII
SN331791VY
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
25-HYDROXYCHOLECALCIFEROL, 5-TRANS-
Common Name English
9,10-SECOCHOLESTA-5,7,10(19)-TRIENE-3,25-DIOL, (3.BETA.,5E,7E)-
Common Name English
CALCIFEDIOL MONOHYDRATE IMPURITY D [EP IMPURITY]
Common Name English
(3S,5E,7E)-9,10-secocholesta-5,7,10(19)-triene-3,25-diol
Systematic Name English
5,6-TRANS-25-HYDROXY VITAMIN D3
Common Name English
25-HYDROXY-5,6-TRANS-CHOLECALCIFEROL
Common Name English
Code System Code Type Description
FDA UNII
SN331791VY
Created by admin on Sat Dec 16 01:53:39 GMT 2023 , Edited by admin on Sat Dec 16 01:53:39 GMT 2023
PRIMARY
ECHA (EC/EINECS)
252-891-2
Created by admin on Sat Dec 16 01:53:39 GMT 2023 , Edited by admin on Sat Dec 16 01:53:39 GMT 2023
PRIMARY
CAS
36149-00-5
Created by admin on Sat Dec 16 01:53:39 GMT 2023 , Edited by admin on Sat Dec 16 01:53:39 GMT 2023
NON-SPECIFIC STEREOCHEMISTRY
PUBCHEM
6506392
Created by admin on Sat Dec 16 01:53:39 GMT 2023 , Edited by admin on Sat Dec 16 01:53:39 GMT 2023
PRIMARY
CAS
1233749-00-2
Created by admin on Sat Dec 16 01:53:39 GMT 2023 , Edited by admin on Sat Dec 16 01:53:39 GMT 2023
PRIMARY
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