Identification

Name
Etidronic acid
Accession Number
DB01077  (APRD00964)
Type
Small Molecule
Groups
Approved
Description

A diphosphonate which affects calcium metabolism. It inhibits ectopic calcification and slows down bone resorption and bone turnover.

Structure
Thumb
Synonyms
  • (1-hydroxy-ethylidene)diphosphonic acid
  • (1-Hydroxyethylene)diphosphonic acid
  • (1-Hydroxyethylidene)bis(phosphonic acid)
  • (1-Hydroxyethylidene)bisphosphonic acid
  • (1-Hydroxyethylidene)diphosphonic acid
  • (Hydroxyethylidene)diphosphonic acid
  • 1-Hydroxy-1,1-diphosphonoethane
  • 1-hydroxyethane 1,1-diphosphonic acid
  • 1-Hydroxyethane-1,1-bisphosphonic acid
  • 1-Hydroxyethane-1,1-diphosphonate
  • 1-Hydroxyethane-1,1-diphosphonic acid
  • 1-Hydroxyethanediphosphonic acid
  • 1-Hydroxyethylidene-1,1-bisphosphonate
  • 1-Hydroxyethylidene-1,1-diphosphonic acid
  • 1,1,1-Ethanetriol diphosphonate
  • Acetodiphosphonic acid
  • acide étidronique
  • ácido etidrónico
  • acidum etidronicum
  • EHDP
  • Ethane-1-hydroxy-1,1-bisphosphonic acid
  • Ethane-1-hydroxy-1,1-diphosphonate
  • Ethane-1-hydroxy-1,1-diphosphonic acid
  • Etidronate
  • Etidronsäure
  • HEDP
  • Hydroxyethanediphosphonic acid
  • Oxyethylidenediphosphonic acid
External IDs
M05BA01 / NSC-227995
Product Ingredients
IngredientUNIICASInChI Key
Etidronate disodiumM16PXG993G7414-83-7GWBBVOVXJZATQQ-UHFFFAOYSA-L
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act EtidronateTablet400 mgOralActavis Pharma CompanyNot applicableNot applicableCanada
Act EtidronateTablet200 mgOralActavis Pharma Company2004-11-10Not applicableCanada
DidronelTablet200 mg/1OralWarner Chilcott1977-01-092010-04-30Us
DidronelTablet400 mg/1OralPhysicians Total Care, Inc.1983-08-122010-06-30Us
DidronelTablet400 mg/1OralWarner Chilcott1983-08-122013-03-01Us
DidronelTablet400 mg/1OralWarner Chilcott2009-11-012013-03-01Us
Didronel Inj 50mg/mlSolution50 mgIntravenousMgi Pharma Inc.1991-12-312004-09-30Canada
Didronel Tab 200mgTablet200 mgOralProcter And Gamble1993-12-312010-07-07Canada
EtidronateTablet400 mgOralCobalt LaboratoriesNot applicableNot applicableCanada
EtidronateTablet200 mgOralCobalt LaboratoriesNot applicableNot applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-etidronateTablet200 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-etidronateTablet400 mgOralApotex CorporationNot applicableNot applicableCanada
Etidronate DisodiumTablet200 mg/1OralGenpharm Ulc2015-11-012015-11-24Us
Etidronate DisodiumTablet200 mg/1OralCarilion Materials Management2008-01-02Not applicableUs
Etidronate DisodiumTablet400 mg/1OralMylan Pharmaceuticals Inc.2008-01-02Not applicableUs
Etidronate DisodiumTablet400 mg/1OralGenpharm Ulc2015-11-012015-11-24Us
Etidronate DisodiumTablet200 mg/1OralMylan Pharmaceuticals Inc.2008-01-022019-11-30Us
Mylan-etidronateTablet200 mgOralMylan Pharmaceuticals2003-06-042017-01-09Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Act EtidrocalEtidronate disodium (400 mg) + Calcium (500 mg)TabletOralActavis Pharma Company2008-04-10Not applicableCanada
DidrocalEtidronate disodium (400 mg) + Calcium (500 mg)Kit; TabletOralWarner Chilcott1995-12-312015-11-19Canada
EtidrocalEtidronate disodium (400 mg) + Calcium (500 mg)TabletOralCobalt LaboratoriesNot applicableNot applicableCanada
EtidrocalEtidronate disodium (400 mg) + Calcium (500 mg)TabletOralSanis Health Inc2010-07-26Not applicableCanada
Mylan-eti-cal CarepacEtidronate disodium (400 mg) + Calcium (500 mg)Kit; TabletOralMylan Pharmaceuticals2008-04-102017-01-09Canada
Novo-etidronatecalEtidronate disodium (400 mg) + Calcium (500 mg)Kit; TabletOralTeva2009-06-15Not applicableCanada
Ntp-etidronate CalciumEtidronate disodium (400 mg) + Calcium (500 mg)Kit; TabletOralTevaNot applicableNot applicableCanada
International/Other Brands
Didronel (Procter & Gamble) / Etidron (Gentili)
Categories
UNII
M2F465ROXU
CAS number
2809-21-4
Weight
Average: 206.0282
Monoisotopic: 205.974525634
Chemical Formula
C2H8O7P2
InChI Key
DBVJJBKOTRCVKF-UHFFFAOYSA-N
InChI
InChI=1S/C2H8O7P2/c1-2(3,10(4,5)6)11(7,8)9/h3H,1H3,(H2,4,5,6)(H2,7,8,9)
IUPAC Name
(1-hydroxy-1-phosphonoethyl)phosphonic acid
SMILES
CC(O)(P(O)(O)=O)P(O)(O)=O

Pharmacology

Indication

For the treatment of symptomatic Paget's disease of bone and in the prevention and treatment of heterotopic ossification following total hip replacement or due to spinal cord injury.

Associated Conditions
Pharmacodynamics

Etidronic acid is a first generation (non-nitrogenous) bisphosphonate in the same family as clodronate and tiludronate. Etidronic acid affects calcium metabolism and inhibits bone resorption and soft tissue calcification. Of the etidronic acid that is resorbed (from oral preparation) or infused (for intravenous drugs), about 50% is excreted unchanged by the kidney. The remainder has a very high affinity for bone tissue, and is rapidly absorbed onto the bone surface. Etidronic acid has been shown to prevent or delay skeletal-related events and decrease bone pain as well as normalize calcium levels in the presence of hypercalcemia.

Mechanism of action

Bisphosphonates, when attached to bone tissue, are absorbed by osteoclasts, the bone cells that breaks down bone tissue. Although the mechanism of action of non-nitrogenous bisphosphonates has not been fully elucidated, available data suggest that they bind strongly to hydroxyapatite crystals in the bone matrix, preferentially at the sites of increased bone turnover and inhibit the formation and dissolution of the crystals. Other actions may include direct inhibition of mature osteoclast function, promotion of osteoclast apoptosis, and interference with osteoblast-mediated osteoclast activation. Etidronic acid does not interfere with bone mineralization. In malignancy-related hypercalcemia, etidronic acid decreases serum calcium by inhibiting tumour-induced bone resorption and reducing calcium flow from the resorbing bone into the blood. Etidronic acid also reduces morbidity of osteolytic bone metastases by inhibiting tumour-induced bone resorption. Etidronic acid may promote osteoclast apoptosis by competing with adenosine triphosphate (ATP) in the cellular energy metabolism. The osteoclast initiates apoptosis and dies, leading to an overall decrease in the breakdown of bone.

TargetActionsOrganism
AAdenosine triphosphate (ATP)
inhibitor
Human
AHydroxylapatite
antagonist
Human
UReceptor-type tyrosine-protein phosphatase S
inhibitor
Human
UV-type proton ATPase catalytic subunit A
inhibitor
Human
Absorption

The amount of drug absorbed after an oral dose is approximately 3%.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Not metabolized.

Route of elimination

Etidronate disodium is not metabolized. Within 24 hours, approximately half the absorbed dose is excreted in urine; the remainder is distributed to bone compartments from which it is slowly eliminated. Unabsorbed drug is excreted intact in the feces.

Half life

In normal subjects, plasma half-life of etidronic acid, based on non-compartmental pharmacokinetics is 1 to 6 hours.

Clearance
Not Available
Toxicity

Clinical experience with acute etidronic acid overdosage is extremely limited. Decreases in serum calcium following substantial overdosage may be expected in some patients. Signs and symptoms of hypocalcemia also may occur in some of these patients. Some patients may develop vomiting. In one event, an 18-year-old female who ingested an estimated single dose of 4800 to 6000 mg (67 to 100 mg/kg) of etidronate was reported to be mildly hypocalcemic (7 .5 2 mg/ dl) and experienced paresthesia of the fingers.

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

Interactions

Drug Interactions
DrugInteraction
AceclofenacThe risk or severity of gastrointestinal bleeding can be increased when Aceclofenac is combined with Etidronic acid.
AcemetacinThe risk or severity of gastrointestinal bleeding can be increased when Acemetacin is combined with Etidronic acid.
Acetylsalicylic acidThe risk or severity of gastrointestinal bleeding can be increased when Acetylsalicylic acid is combined with Etidronic acid.
AcyclovirThe risk or severity of nephrotoxicity and hypocalcemia can be increased when Acyclovir is combined with Etidronic acid.
AdefovirThe risk or severity of nephrotoxicity and hypocalcemia can be increased when Adefovir is combined with Etidronic acid.
Adefovir DipivoxilThe risk or severity of nephrotoxicity and hypocalcemia can be increased when Adefovir Dipivoxil is combined with Etidronic acid.
AlclofenacThe risk or severity of gastrointestinal bleeding can be increased when Alclofenac is combined with Etidronic acid.
Alendronic acidThe risk or severity of hypocalcemia can be increased when Alendronic acid is combined with Etidronic acid.
AlmasilateThe serum concentration of Etidronic acid can be decreased when it is combined with Almasilate.
AlminoprofenThe risk or severity of gastrointestinal bleeding can be increased when Alminoprofen is combined with Etidronic acid.
Food Interactions
  • Avoid aluminium, calcium, iron and magnesium within 2 hours of taking medication.
  • Take on an empty stomach with a full glass of water.

References

Synthesis Reference

Rogovin, L.,Brawn, D.P. and Kalberg, AN.; US. Patent 3,400,147; September 3,1968; assigned to The Procter & Gamble Co.

General References
Not Available
External Links
Human Metabolome Database
HMDB0015210
KEGG Drug
D02373
KEGG Compound
C07736
PubChem Compound
3305
PubChem Substance
46507694
ChemSpider
3189
BindingDB
50115102
ChEBI
4907
ChEMBL
CHEMBL871
Therapeutic Targets Database
DNC000629
PharmGKB
PA449548
HET
911
RxList
RxList Drug Page
Wikipedia
Etidronic_acid
ATC Codes
M05BB01 — Etidronic acid and calcium, sequentialM05BA01 — Etidronic acid
AHFS Codes
  • 92:24.00 — Bone Resorption Inhibitors
  • 92:00.00 — Miscellaneous Therapeutic Agents
PDB Entries
3sdv
FDA label
Download (42 KB)
MSDS
Download (44.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2RecruitingTreatmentArterial Calcification / Arterial Calcification Due to CD73-Deficiency (ACDC) / CD73 Deficiency1
4CompletedTreatmentOsteoporosis1
Not AvailableCompletedNot AvailableAdenocarcinomas / Esophageal Cancers / Squamous Cell Carcinoma (SCC)1
Not AvailableEnrolling by InvitationNot AvailableAtypical Femoral Fractures / Bisphosphonate Therapy / Osteoporosis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Genpharm LP
  • MGI Pharma
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Norwich Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Procter & Gamble
  • Warner Chilcott Co. Inc.
  • WC Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral
TabletOral200 mg
TabletOral400 mg
TabletOral200 mg/1
TabletOral400 mg/1
SolutionIntravenous50 mg
Kit; tabletOral
Prices
Unit descriptionCostUnit
Didronel 400 mg tablet8.31USD tablet
Didronel 200 mg tablet4.16USD tablet
Co Etidronate 200 mg Tablet0.86USD tablet
Mylan-Etidronate 200 mg Tablet0.86USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP-3.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility11.5 mg/mLALOGPS
logP-0.77ALOGPS
logP-2.3ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)0.7ChemAxon
pKa (Strongest Basic)-5.1ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area135.29 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity34.51 m3·mol-1ChemAxon
Polarizability13.97 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8918
Blood Brain Barrier+0.8901
Caco-2 permeable-0.8581
P-glycoprotein substrateNon-substrate0.7483
P-glycoprotein inhibitor INon-inhibitor0.9639
P-glycoprotein inhibitor IINon-inhibitor0.9951
Renal organic cation transporterNon-inhibitor0.9726
CYP450 2C9 substrateNon-substrate0.7545
CYP450 2D6 substrateNon-substrate0.8473
CYP450 3A4 substrateNon-substrate0.6987
CYP450 1A2 substrateNon-inhibitor0.9061
CYP450 2C9 inhibitorNon-inhibitor0.9047
CYP450 2D6 inhibitorNon-inhibitor0.9222
CYP450 2C19 inhibitorNon-inhibitor0.9186
CYP450 3A4 inhibitorNon-inhibitor0.9595
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9873
Ames testNon AMES toxic0.8875
CarcinogenicityCarcinogens 0.5282
BiodegradationNot ready biodegradable0.7701
Rat acute toxicity1.9653 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9519
hERG inhibition (predictor II)Non-inhibitor0.9495
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0a4i-0090000000-a9f75f8364e22febc69e
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0a4i-0190000000-7e7c121eec680994473e
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0a4i-0390000000-f6ab7574deae5f44d8b4
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-08j0-9620000000-0618a9cfbf1724258f3b
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-03di-9100000000-cfaba7073e26e33fa329

Taxonomy

Description
This compound belongs to the class of organic compounds known as bisphosphonates. These are organic compounds containing two phosphonate groups linked together through a carbon atoms.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Organic phosphonic acids and derivatives
Sub Class
Bisphosphonates
Direct Parent
Bisphosphonates
Alternative Parents
Organic phosphonic acids / Organopnictogen compounds / Organophosphorus compounds / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Bisphosphonate / Organophosphonic acid / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative / Organophosphorus compound / Organooxygen compound / Aliphatic acyclic compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
1,1-bis(phosphonic acid) (CHEBI:4907)

Targets

Kind
Small molecule
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
References
  1. Rogers MJ, Crockett JC, Coxon FP, Monkkonen J: Biochemical and molecular mechanisms of action of bisphosphonates. Bone. 2011 Jul;49(1):34-41. doi: 10.1016/j.bone.2010.11.008. Epub 2010 Nov 26. [PubMed:21111853]
Kind
Small molecule
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
References
  1. Grases F, Sanchis P, Perello J, Isern B, Prieto RM, Fernandez-Palomeque C, Torres JJ: Effect of crystallization inhibitors on vascular calcifications induced by vitamin D: a pilot study in Sprague-Dawley rats. Circ J. 2007 Jul;71(7):1152-6. [PubMed:17587727]
  2. Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, Mangood A, Russell RG, Ebetino FH: Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006 May;38(5):617-27. Epub 2005 Jul 20. [PubMed:16046206]
  3. Ono K, Wada S: [Regulation of calcification by bisphosphonates]. Clin Calcium. 2004 Jun;14(6):60-3. [PubMed:15577056]
  4. Takaishi Y: [Treatment of periodontal disease, prevention and bisphosphonate]. Clin Calcium. 2003 Feb;13(2):173-6. [PubMed:15775080]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine phosphatase activity
Specific Function
Interacts with LAR-interacting protein LIP.1.
Gene Name
PTPRS
Uniprot ID
Q13332
Uniprot Name
Receptor-type tyrosine-protein phosphatase S
Molecular Weight
217039.825 Da
References
  1. Schmidt A, Rutledge SJ, Endo N, Opas EE, Tanaka H, Wesolowski G, Leu CT, Huang Z, Ramachandaran C, Rodan SB, Rodan GA: Protein-tyrosine phosphatase activity regulates osteoclast formation and function: inhibition by alendronate. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3068-73. [PubMed:8610169]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Proton-transporting atpase activity, rotational mechanism
Specific Function
Catalytic subunit of the peripheral V1 complex of vacuolar ATPase. V-ATPase vacuolar ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells.
Gene Name
ATP6V1A
Uniprot ID
P38606
Uniprot Name
V-type proton ATPase catalytic subunit A
Molecular Weight
68303.5 Da
References
  1. David P, Nguyen H, Barbier A, Baron R: The bisphosphonate tiludronate is a potent inhibitor of the osteoclast vacuolar H(+)-ATPase. J Bone Miner Res. 1996 Oct;11(10):1498-507. [PubMed:8889850]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:49