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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
Structure for Doxercalciferol (DB06410)
- 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.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Secondary hyperparathyroidism •••••••••••• •••••••••• •••••••••• •••••••• Treatment of Secondary hyperparathyroidism •••••••••••• Treatment of Secondary hyperparathyroidism •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism UVitamin D3 receptor suppressorHumans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAcetyldigitoxin The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Doxercalciferol is combined with Acetyldigitoxin. Alfacalcidol The risk or severity of adverse effects can be increased when Alfacalcidol is combined with Doxercalciferol. Aluminum hydroxide The serum concentration of Aluminum hydroxide can be increased when it is combined with Doxercalciferol. Beclomethasone dipropionate The therapeutic efficacy of Doxercalciferol can be decreased when used in combination with Beclomethasone dipropionate. Bendroflumethiazide The risk or severity of hypercalcemia can be increased when Bendroflumethiazide is combined with Doxercalciferol. - Food Interactions
- Avoid antacids. Specifically, avoid magnesium-containing antacids as co-administration with doxercalciferol increases the risk of hypermagnesemia.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Hectoral (Genzyme)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Doxercalciferol Injection, solution 2 ug/1mL Intravenous Hospira, Inc. 2019-10-24 2019-10-24 US 
Doxercalciferol Injection, solution 2 ug/1mL Intravenous Hospira, Inc. 2019-10-24 Not applicable US Hectorol Injection, solution 4 ug/2mL Intravenous Genzyme Corporation 2006-07-20 2006-07-20 US Hectorol Capsule, liquid filled 2.5 ug/1 Oral Genzyme Corporation 2009-08-03 2019-01-31 US Hectorol Capsule, liquid filled 0.5 ug/1 Oral Remedy Repack 2012-07-24 2013-12-12 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Doxercalciferol Capsule 0.5 ug/1 Oral Rising Pharmaceuticals, Inc. 2016-09-09 Not applicable US Doxercalciferol Injection, solution 2 ug/1mL Intravenous Eugia US LLC 2022-01-24 Not applicable US Doxercalciferol Capsule 1 ug/1 Oral Winthrop U.S, a business of sanofi-aventis U.S. LLC 2017-04-17 Not applicable US Doxercalciferol Capsule 0.5 ug/1 Oral Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc. 2020-10-31 Not applicable US Doxercalciferol Injection, solution 4 ug/2mL Intravenous Gland Pharma Limited 2019-09-26 Not applicable US
Categories
- ATC Codes
- H05BX03 — Doxercalciferol
- Drug Categories
- Anti-Parathyroid Agents
- Bone Density Conservation Agents
- Calcium Homeostasis
- Cholestanes
- Cholestenes
- Diet, Food, and Nutrition
- Food
- Fused-Ring Compounds
- Lipids
- Membrane Lipids
- Micronutrients
- Physiological Phenomena
- Secosteroids
- Steroids
- Sterols
- Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins
- Vitamin D and Analogues
- Vitamins
- Vitamins (Fat Soluble)
- 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
- 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]
- 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]
- FDA Approved Drug Products: HECTOROL (doxercalciferol) capsules and injection [Link]
- External Links
- KEGG Drug
- D01009
- KEGG Compound
- C08211
- PubChem Compound
- 46705423
- PubChem Substance
- 347827769
- ChemSpider
- 4444554
- 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
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data4 Completed Treatment Chronic Kidney Disease (CKD) / Hemodialysis Treatment / Secondary Hyperparathyroidism (SHPT) 1 somestatus stop reason just information to hide 4 Completed Treatment Chronic Kidney Disease (CKD) / Kidney Transplantation 1 somestatus stop reason just information to hide 4 Completed Treatment Kidney Failure / Renal Insufficiency,Chronic / Secondary Hyperparathyroidism (SHPT) 1 somestatus stop reason just information to hide 4 Completed Treatment Renal Failure, Chronic Renal Failure / Secondary Hyperparathyroidism (SHPT) 1 somestatus stop reason just information to hide 4 Completed Treatment Secondary Hyperparathyroidism (SHPT) 4 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 0.5 ug/1 Capsule Oral 1 ug/1 Capsule Oral 2.5 ug/1 Injection Intravenous 2 ug/1mL Injection Intravenous 4 ug/2mL Capsule Oral 0.5 mcg Capsule Oral 2.5 mcg Capsule, liquid filled Oral 0.5 ug/1 Capsule, liquid filled Oral 1 ug/1 Capsule, liquid filled Oral 2.5 ug/1 Injection, solution Intravenous 2 ug/1mL Injection, solution Intravenous 4 ug/2mL Capsule, liquid filled Oral 2.5 cg Capsule, liquid filled Oral 0.5 cg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7148211 No 2006-12-12 2023-09-14 US US5707980 No 1998-01-13 2010-08-17 US US6903083 No 2005-06-07 2021-07-18 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Relatively insoluble FDA Label - Predicted Properties
Property Value Source Water Solubility 0.00168 mg/mL ALOGPS logP 6.27 ALOGPS logP 5.75 Chemaxon logS -5.4 ALOGPS pKa (Strongest Acidic) 14.39 Chemaxon pKa (Strongest Basic) -2.8 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 40.46 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 130.36 m3·mol-1 Chemaxon Polarizability 51.58 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-0198100000-a475c303df01179fc4d0 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-0100900000-114aa82f080b27f22319 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-01pc-1209300000-6d8fd3dc52a018ab65a1 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-5197000000-684d3b0e6209df6c1794 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0551-2509000000-1899afe3da934aaeb13f Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0089-8793000000-083aee4cb4dad0b5fbdf Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 226.4492892 predictedDarkChem Lite v0.1.0 [M-H]- 221.36217 predictedDeepCCS 1.0 (2019) [M+H]+ 227.4374892 predictedDarkChem Lite v0.1.0 [M+H]+ 223.08588 predictedDeepCCS 1.0 (2019) [M+Na]+ 226.3502892 predictedDarkChem Lite v0.1.0 [M+Na]+ 229.41484 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Suppressor
- General Function
- Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells (PubMed:10678179, PubMed:15728261, PubMed:16913708, PubMed:28698609, PubMed:37478846). Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR (PubMed:28698609). The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes (PubMed:28698609). Plays a central role in calcium homeostasis (By similarity). Also functions as a receptor for the secondary bile acid lithocholic acid (LCA) and its metabolites (PubMed:12016314, PubMed:32354638)
- Specific Function
- Bile acid nuclear receptor activity
- Gene Name
- VDR
- Uniprot ID
- P11473
- Uniprot Name
- Vitamin D3 receptor
- Molecular Weight
- 48288.64 Da
References
- 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
- Cytochrome P450 monooxygenase that catalyzes regio- and stereospecific hydroxylation of cholesterol and its derivatives. Hydroxylates (with R stereochemistry) the terminal methyl group of cholesterol side-chain in a three step reaction to yield at first a C26 alcohol, then a C26 aldehyde and finally a C26 acid (PubMed:12077124, PubMed:21411718, PubMed:28190002, PubMed:9660774). Regulates cholesterol homeostasis by catalyzing the conversion of excess cholesterol to bile acids via both the 'neutral' (classic) and the 'acid' (alternative) pathways (PubMed:11412116, PubMed:1708392, PubMed:2019602, PubMed:7915755, PubMed:9186905, PubMed:9660774, PubMed:9790667). May also regulate cholesterol homeostasis via generation of active oxysterols, which act as ligands for NR1H2 and NR1H3 nuclear receptors, modulating the transcription of genes involved in lipid metabolism (PubMed:12077124, PubMed:9660774). Plays a role in cholestanol metabolism in the cerebellum. Similarly to cholesterol, hydroxylates cholestanol and may facilitate sterol diffusion through the blood-brain barrier to the systemic circulation for further degradation (PubMed:28190002). Also hydroxylates retinal 7-ketocholesterol, a noxious oxysterol with pro-inflammatory and pro-apoptotic effects, and may play a role in its elimination from the retinal pigment epithelium (PubMed:21411718). May play a redundant role in vitamin D biosynthesis. Catalyzes 25-hydroxylation of vitamin D3 that is required for its conversion to a functionally active form (PubMed:15465040)
- Specific Function
- 3-alpha,7-alpha,12-alpha-trihydroxycholestan-26-al 26-oxidoreductase activity
- Gene Name
- CYP27A1
- Uniprot ID
- Q02318
- Uniprot Name
- Sterol 26-hydroxylase, mitochondrial
- Molecular Weight
- 60234.28 Da
References
- 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