Identification

Name
Doxercalciferol
Accession Number
DB06410
Type
Small Molecule
Groups
Approved
Description

Doxercalciferol is a synthetic vitamin D2 analog that undergoes metabolic activation in vivo to form 1α,25-dihydroxyvitamin D2 (1α,25-(OH)2D2), a naturally occurring, biologically active form of vitamin D2. Doxercalciferol is indicated for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, as well as for the treatment of secondary hyperparathyroidism in patients with Stage 3 or Stage 4 chronic kidney disease. Doxercalciferol is marketed under the brand name Hectoral by Genzyme Corporation, and is manufactured by Catalent Pharma Solutions, Inc.

Structure
Thumb
Synonyms
  • (1S,3R,5Z,7E,22E)-9,10-Secoergosta-5,7,10,22-tetraene-1,3-diol
  • 1-alpha-hydroxyergocalciferol
  • 1-Hydroxyergocalciferol
  • 1-Hydroxyvitamin D2
  • 1alpha-hydroxyvitamin D2
  • 1α-Hydroxyergocalciferol
  • Doxercalciferol
  • Doxercalciferolum
External IDs
BRN 4716774 / TSA 840 / TSA-840
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DoxercalciferolCapsule0.5 ug/1OralWinthrop U.S.2017-04-17Not applicableUs
DoxercalciferolCapsule2.5 ug/1OralWinthrop U.S.2017-04-17Not applicableUs
DoxercalciferolCapsule1 ug/1OralWinthrop U.S.2017-04-17Not applicableUs
HectorolInjection, solution4 ug/2mLIntravenousGenzyme Corporation2008-12-08Not applicableUs
HectorolCapsule2.5 mcgOralSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2001-09-262008-10-30Canada
HectorolCapsule, liquid filled1 ug/1OralGenzyme Corporation2009-08-032019-01-31Us
HectorolInjection, solution4 ug/2mLIntravenousGenzyme Corporation2006-07-202006-07-20Us
HectorolInjection, solution2 ug/1mLIntravenousGenzyme Corporation2008-12-08Not applicableUs
HectorolCapsule, liquid filled2.5 ug/1OralGenzyme Corporation2009-08-032019-01-31Us
HectorolCapsule, liquid filled0.5 ug/1OralRemedy Repack2012-07-242013-12-12Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DoxercalciferolInjection, solution2 ug/1mLIntravenousSandoz2014-09-042014-09-04Us
DoxercalciferolCapsule2.5 ug/1OralWest-Ward Pharmaceuticals Corp.2014-02-18Not applicableUs
DoxercalciferolInjection2 ug/1mLIntravenousWest Ward Pharmaceutical2013-08-30Not applicableUs
DoxercalciferolCapsule2.5 ug/1OralRising Pharmaceuticals2016-09-09Not applicableUs
DoxercalciferolCapsule0.5 ug/1OralRising Pharmaceuticals2016-09-09Not applicableUs
DoxercalciferolInjection, solution2 ug/1mLIntravenousAmneal Biosciences2017-05-24Not applicableUs
DoxercalciferolInjection, solution4 ug/2mLIntravenousAkorn2015-05-08Not applicableUs
DoxercalciferolCapsule, liquid filled0.5 ug/1OralPrasco Laboratories2014-01-142019-01-31Us
DoxercalciferolCapsule1 ug/1OralWest-Ward Pharmaceuticals Corp.2014-02-18Not applicableUs
DoxercalciferolCapsule, liquid filled2.5 ug/1OralAvera McKennan Hospital2015-04-062018-06-07Us
International/Other Brands
Hectoral (Genzyme)
Categories
UNII
3DIZ9LF5Y9
CAS number
54573-75-0
Weight
Average: 412.6478
Monoisotopic: 412.334130652
Chemical Formula
C28H44O2
InChI Key
HKXBNHCUPKIYDM-CGMHZMFXSA-N
InChI
InChI=1S/C28H44O2/c1-18(2)19(3)9-10-20(4)25-13-14-26-22(8-7-15-28(25,26)6)11-12-23-16-24(29)17-27(30)21(23)5/h9-12,18-20,24-27,29-30H,5,7-8,13-17H2,1-4,6H3/b10-9+,22-11+,23-12-/t19-,20+,24+,25+,26-,27-,28+/m0/s1
IUPAC Name
(1R,3S,5Z)-5-{2-[(1R,3aS,4E,7aR)-1-[(2R,3E,5R)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylidenecyclohexane-1,3-diol
SMILES
[H]\C(\C(\[H])=C1/CCC[C@@]2(C)[C@@]1([H])CC[C@]2([H])[C@]([H])(C)C(\[H])=C(/[H])[C@]([H])(C)C(C)C)=C1/C[C@@]([H])(O)C[C@]([H])(O)C1=C

Pharmacology

Indication

Doxercalciferol is indicated for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, as well as for the treatment of secondary hyperparathyroidism in patients with Stage 3 or Stage 4 chronic kidney disease.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Calcitriol (1α,25-(OH)2D3) and 1α,25-(OH)2D2 regulate blood calcium at levels required for essential body functions. Specifically, the biologically active vitamin D metabolites control the intestinal absorption of dietary calcium, the tubular reabsorption of calcium by the kidney and, in conjunction with parathyroid hormone (PTH), the mobilization of calcium from the skeleton. They act directly on bone cells (osteoblasts) to stimulate skeletal growth, and on the parathyroid glands to suppress PTH (parathyroid hormone) synthesis and secretion. These functions are mediated by the interaction of these biologically active metabolites with specific receptor proteins in the various target tissues. In patients with chronic kidney disease (CKD), deficient production of biologically active vitamin D metabolites (due to lack of or insufficient 25-hydroxyvitamin D-1-alpha-hydroxylase activity) leads to secondary hyperparathyroidism, which contributes to the development of metabolic bone disease.

TargetActionsOrganism
UVitamin D3 receptor
suppressor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Doxercalciferol is absorbed from the gastrointestinal tract and activated by CYP 27 in the liver to form 1α,25-(OH)2D2 (major metabolite) and 1α,24-dihydroxyvitamin D2 (minor metabolite). Activation of doxercalciferol does not require the involvement of the kidneys.

Route of elimination
Not Available
Half life

32 to 37 hours.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1alpha-Hydroxyvitamin D5The risk or severity of adverse effects can be increased when Doxercalciferol is combined with 1alpha-Hydroxyvitamin D5.
AcetyldigitoxinThe risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Doxercalciferol is combined with Acetyldigitoxin.
AcetyldigoxinThe risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Doxercalciferol is combined with Acetyldigoxin.
AldosteroneThe therapeutic efficacy of Doxercalciferol can be decreased when used in combination with Aldosterone.
AlfacalcidolThe risk or severity of adverse effects can be increased when Alfacalcidol is combined with Doxercalciferol.
Aluminum hydroxideThe serum concentration of Aluminum hydroxide can be increased when it is combined with Doxercalciferol.
Beclomethasone dipropionateThe therapeutic efficacy of Doxercalciferol can be decreased when used in combination with Beclomethasone dipropionate.
BecocalcidiolThe risk or severity of adverse effects can be increased when Becocalcidiol is combined with Doxercalciferol.
BendroflumethiazideThe risk or severity of hypercalcemia can be increased when Bendroflumethiazide is combined with Doxercalciferol.
BenzthiazideThe risk or severity of hypercalcemia can be increased when Benzthiazide is combined with Doxercalciferol.
Food Interactions
Not Available

References

Synthesis Reference

"Patent Link":http://www.google.ca/patents/US7148211

General References
  1. Dheerendra PC, Sakhuja V, Kohli HS, Jha V: Efficacy and safety of oral doxercalciferol in the management of secondary hyperparathyroidism in chronic kidney disease stage 4. Indian J Nephrol. 2013 Jul;23(4):271-5. doi: 10.4103/0971-4065.114492. [PubMed:23960343]
  2. Ritter CS, Brown AJ: Direct suppression of Pth gene expression by the vitamin D prohormones doxercalciferol and calcidiol requires the vitamin D receptor. J Mol Endocrinol. 2011 Feb 15;46(2):63-6. doi: 10.1677/JME-10-0128. Print 2011 Apr. [PubMed:21169421]
External Links
KEGG Drug
D01009
KEGG Compound
C08211
PubChem Compound
46705423
PubChem Substance
347827769
ChemSpider
4444554
ChEBI
4712
ChEMBL
CHEMBL1200810
HET
V2H
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Doxercalciferol
ATC Codes
H05BX03 — Doxercalciferol
PDB Entries
3dl9
FDA label
Download (96 KB)
MSDS
Download (39.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentChronic Kidney Disease (CKD) / Chronic Renal Failure (CRF) / Hyperparathyroidism, Secondary / Renal Insufficiency,Chronic1
1TerminatedTreatmentTumors, Solid1
2CompletedTreatmentHyperparathyroidism, Secondary / Renal Osteodystrophy1
2CompletedTreatmentModerate to Severe Chronic Plaque Psoriasis1
2TerminatedTreatmentProstate Cancer1
3CompletedTreatmentChronic Kidney Disease (CKD) / Deficiency, Vitamin D / Hyperparathyroidism, Secondary1
3RecruitingTreatmentSecondary Hyperparathyroidism-Chronic Kidney Disease1
4CompletedTreatmentChronic Kidney Disease (CKD) / Hemodialysis Treatment / Hyperparathyroidism, Secondary1
4CompletedTreatmentChronic Kidney Disease, Stage 5 / Hyperparathyroidism, Secondary1
4CompletedTreatmentChronic Renal Failure (CRF) / Hyperparathyroidism, Secondary1
4CompletedTreatmentHyperparathyroidism, Secondary4
4CompletedTreatmentHyperparathyroidism, Secondary / Renal Failure / Renal Insufficiency,Chronic1
4TerminatedTreatmentHyperparathyroidism, Secondary1
4Unknown StatusTreatmentChronic Kidney Disease (CKD) / Transplantation, Kidney1
4WithdrawnPreventionCoronary Calcification / Endstage Renal Disease / Parathyroid Hormone1
Not AvailableCompletedTreatmentRenal Osteodystrophy / Secondary Hyperparathyroidism in Chronic Kidney Disease Stage 3 and 41

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral0.5 ug/1
CapsuleOral1 ug/1
CapsuleOral2.5 ug/1
Capsule, liquid filledOral2.5 ug/1
InjectionIntravenous2 ug/1mL
CapsuleOral2.5 mcg
Capsule, liquid filledOral0.5 ug/1
Capsule, liquid filledOral1 ug/1
Injection, solutionIntravenous2 ug/1mL
Injection, solutionIntravenous4 ug/2mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7148211No2003-09-142023-09-14Us
US5707980No1993-08-172010-08-17Us
US6903083No2001-07-182021-07-18Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityRelatively insolubleFDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.00168 mg/mLALOGPS
logP6.27ALOGPS
logP5.75ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)14.39ChemAxon
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity130.36 m3·mol-1ChemAxon
Polarizability52.01 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as vitamin d and derivatives. These are compounds containing a secosteroid backbone, usually secoergostane or secocholestane.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Vitamin D and derivatives
Direct Parent
Vitamin D and derivatives
Alternative Parents
Triterpenoids / Secondary alcohols / Cyclic alcohols and derivatives / Hydrocarbon derivatives
Substituents
Triterpenoid / Cyclic alcohol / Secondary alcohol / Organic oxygen compound / Hydrocarbon derivative / Organooxygen compound / Alcohol / Aliphatic homopolycyclic compound
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
vitamin D (CHEBI:4712) / Vitamin D2 and derivatives (LMST03010028)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Suppressor
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Recruited to promoters via its interaction with BAZ1B...
Gene Name
VDR
Uniprot ID
P11473
Uniprot Name
Vitamin D3 receptor
Molecular Weight
48288.64 Da
References
  1. Ritter CS, Brown AJ: Direct suppression of Pth gene expression by the vitamin D prohormones doxercalciferol and calcidiol requires the vitamin D receptor. J Mol Endocrinol. 2011 Feb 15;46(2):63-6. doi: 10.1677/JME-10-0128. Print 2011 Apr. [PubMed:21169421]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
Activator
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Catalyzes the first step in the oxidation of the side chain of sterol intermediates; the 27-hydroxylation of 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol. Has also a vitamin D3-25-hydroxylase a...
Gene Name
CYP27A1
Uniprot ID
Q02318
Uniprot Name
Sterol 26-hydroxylase, mitochondrial
Molecular Weight
60234.28 Da
References
  1. Dheerendra PC, Sakhuja V, Kohli HS, Jha V: Efficacy and safety of oral doxercalciferol in the management of secondary hyperparathyroidism in chronic kidney disease stage 4. Indian J Nephrol. 2013 Jul;23(4):271-5. doi: 10.4103/0971-4065.114492. [PubMed:23960343]

Drug created on March 19, 2008 10:30 / Updated on November 02, 2018 06:16