Identification

Summary

Doxercalciferol is a synthetic vitamin D2 analog used to treat secondary hyperparathyroidism in patients with chronic kidney disease with or without therapy of dialysis.

Brand Names
Hectorol
Generic Name
Doxercalciferol
DrugBank Accession Number
DB06410
Background

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.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 412.6478
Monoisotopic: 412.334130652
Chemical Formula
C28H44O2
Synonyms
  • (1S,3R,5Z,7E,22E)-9,10-Secoergosta-5,7,10,22-tetraene-1,3-diol
  • 1-Hydroxyergocalciferol
  • 1-Hydroxyvitamin D2
  • 1α-Hydroxyergocalciferol
  • 1α-hydroxyvitamin D2
  • Doxercalciferol
  • Doxercalciferolum
  • Doxercalciférolum
External IDs
  • BRN 4716774
  • TSA 840
  • TSA-840

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.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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
Humans
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

Adverse Effects
Adverseeffects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcetyldigitoxinThe risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Doxercalciferol is combined with Acetyldigitoxin.
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.
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.
BetamethasoneThe therapeutic efficacy of Doxercalciferol can be decreased when used in combination with Betamethasone.
Betamethasone phosphateThe therapeutic efficacy of Doxercalciferol can be decreased when used in combination with Betamethasone phosphate.
BudesonideThe therapeutic efficacy of Doxercalciferol can be decreased when used in combination with Budesonide.
CalcifediolThe risk or severity of adverse effects can be increased when Calcifediol is combined with Doxercalciferol.
Interactions
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Food Interactions
  • Avoid antacids. Specifically, avoid magnesium-containing antacids as co-administration with doxercalciferol increases the risk of hypermagnesemia.

Products

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International/Other Brands
Hectoral (Genzyme)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DoxercalciferolInjection, solution2 ug/1mLIntravenousHospira, Inc.2019-10-242019-10-24US flag
DoxercalciferolInjection, solution2 ug/1mLIntravenousHospira, Inc.2019-10-24Not applicableUS flag
HectorolInjection, solution4 ug/2mLIntravenousGenzyme Corporation2008-12-08Not applicableUS flag
HectorolCapsule, liquid filled0.5 ug/1OralGenzyme Corporation2009-08-032019-01-31US flag
HectorolInjection, solution4 ug/2mLIntravenousGenzyme Corporation2008-12-08Not applicableUS flag
HectorolCapsule, liquid filled1 ug/1OralGenzyme Corporation2009-08-032019-01-31US flag
HectorolCapsule2.5 mcgOralSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2001-09-262008-10-30Canada flag
HectorolInjection, solution4 ug/2mLIntravenousGenzyme Corporation2006-07-202006-07-20US flag
HectorolInjection, solution2 ug/1mLIntravenousGenzyme Corporation2008-12-082021-04-30US flag
HectorolCapsule, liquid filled2.5 ug/1OralGenzyme Corporation2009-08-032019-01-31US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DoxercalciferolCapsule, liquid filled0.5 ug/1OralPrasco Laboratories2014-01-142019-01-31US flag
DoxercalciferolCapsule2.5 ug/1OralWest-Ward Pharmaceuticals Corp.2014-02-18Not applicableUS flag
DoxercalciferolCapsule1 ug/1OralWinthrop U.S.2017-04-17Not applicableUS flag
DoxercalciferolCapsule1 ug/1OralHeritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.2020-10-31Not applicableUS flag
DoxercalciferolCapsule0.5 ug/1OralAmerican Health Packaging2015-11-032020-03-31US flag
DoxercalciferolCapsule1 ug/1OralRising Pharmaceuticals2016-09-09Not applicableUS flag
DoxercalciferolInjection, solution4 ug/2mLIntravenousGland Pharma Limited2019-09-26Not applicableUS flag
DoxercalciferolInjection, solution4 ug/2mLIntravenousMeitheal Pharmaceuticals Inc.2020-02-11Not applicableUS flag
DoxercalciferolInjection, solution4 ug/2mLIntravenousSandoz Inc2014-02-042017-08-31US flag
DoxercalciferolInjection, solution4 ug/2mLIntravenousGland Pharma Limited2019-09-26Not applicableUS flag

Categories

ATC Codes
H05BX03 — Doxercalciferol
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Alcohol / Aliphatic homopolycyclic compound / Cyclic alcohol / Hydrocarbon derivative / Organic oxygen compound / Organooxygen compound / Secondary alcohol / Triterpenoid
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
vitamin D (CHEBI:4712) / Vitamin D2 and derivatives (LMST03010028)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
3DIZ9LF5Y9
CAS number
54573-75-0
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@@]1(CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C)[C@H](C)\C=C\[C@H](C)C(C)C

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. [Article]
  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. [Article]
  3. FDA Approved Drug Products: HECTOROL (doxercalciferol) capsules and injection [Link]
KEGG Drug
D01009
KEGG Compound
C08211
PubChem Compound
46705423
PubChem Substance
347827769
ChemSpider
4444554
RxNav
11516
ChEBI
4712
ChEMBL
CHEMBL1200810
ZINC
ZINC000004641374
PDBe Ligand
V2H
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Doxercalciferol
PDB Entries
3dl9
FDA label
Download (96 KB)
MSDS
Download (39.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentChronic Kidney Disease (CKD) / Hemodialysis Treatment / Secondary Hyperparathyroidism (SHPT)1
4CompletedTreatmentChronic Kidney Disease (CKD) / Kidney Transplantation1
4CompletedTreatmentHemodialysis-dependent chronic kidney disease (HDD-CKD) / Secondary Hyperparathyroidism (SHPT)1
4CompletedTreatmentKidney Failure / Renal Insufficiency,Chronic / Secondary Hyperparathyroidism (SHPT)1
4CompletedTreatmentRenal Failure, Chronic Renal Failure / Secondary Hyperparathyroidism (SHPT)1
4CompletedTreatmentSecondary Hyperparathyroidism (SHPT)4
4TerminatedTreatmentSecondary Hyperparathyroidism (SHPT)1
4WithdrawnPreventionCoronary Calcification / End Stage Renal Disease (ESRD) / Parathyroid Hormone1
3CompletedTreatmentChronic Kidney Disease (CKD) / Deficiency, Vitamin D / Secondary Hyperparathyroidism (SHPT)1
3RecruitingTreatmentSecondary Hyperparathyroidism, Chronic Kidney Disease1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral0.5 ug/1
CapsuleOral1 ug/1
CapsuleOral2.5 ug/1
InjectionIntravenous2 ug/1mL
InjectionIntravenous4 ug/2mL
CapsuleOral2.5 mcg
Capsule, liquid filledOral0.5 ug/1
Capsule, liquid filledOral1 ug/1
Capsule, liquid filledOral2.5 ug/1
Injection, solutionIntravenous2 ug/1mL
Injection, solutionIntravenous4 ug/2mL
Capsule, liquid filledOral2.5 cg
Capsule, liquid filledOral0.5 cg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7148211No2006-12-122023-09-14US flag
US5707980No1998-01-132010-08-17US flag
US6903083No2005-06-072021-07-18US flag

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
Polarizability51.58 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

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
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. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Substrate
Curator comments
Doxercalciferol requires activation by CYP 27 in the liver to form 1α,25-(OH)2D2 (major metabolite) and 1α,24-dihydroxyvitamin D2 (minor metabolite).
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. [Article]

Drug created at March 19, 2008 16:30 / Updated at October 07, 2021 12:08