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Identification
NameEtidronic acid
Accession NumberDB01077  (APRD00964)
TypeSmall Molecule
GroupsApproved
Description

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

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 Identifiers
  • NSC-227995
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act Etidronatetablet400 mgoralActavis Pharma CompanyNot applicableNot applicableCanada
Act Etidronatetablet200 mgoralActavis Pharma Company2004-11-10Not applicableCanada
Didronel Inj 50mg/mlsolution50 mgintravenousMgi Pharma Inc.1991-12-312004-09-30Canada
Didronel Tab 200mgtablet200 mgoralProcter & Gamble Pharmaceuticals Canada Inc1993-12-312010-07-07Canada
Etidronatetablet400 mgoralCobalt Pharmaceuticals CompanyNot applicableNot applicableCanada
Etidronatetablet200 mgoralCobalt Pharmaceuticals CompanyNot applicableNot applicableCanada
Mylan-etidronatetablet200 mgoralMylan Pharmaceuticals Ulc2003-06-04Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-etidronatetablet400 mgoralApotex IncNot applicableNot applicableCanada
Apo-etidronatetablet200 mgoralApotex IncNot applicableNot applicableCanada
Etidronate Disodiumtablet200 mg/1oralMylan Pharmaceuticals Inc.2008-01-022016-04-23Us
Etidronate Disodiumtablet200 mg/1oralCarilion Materials Management2008-01-022016-04-05Us
Etidronate Disodiumtablet400 mg/1oralMylan Pharmaceuticals Inc.2008-01-022016-04-23Us
Over the Counter ProductsNot Available
International Brands
NameCompany
DidronelProcter & Gamble
EtidronGentili
Brand mixtures
NameLabellerIngredients
Act EtidrocalActavis Pharma Company
DidrocalWarner Chilcott Canada Co
EtidrocalSanis Health Inc
Mylan-eti-cal CarepacMylan Pharmaceuticals Ulc
Novo-etidronatecalTeva Canada Limited
Ntp-etidronate CalciumTeva Canada Limited
Salts
Name/CASStructureProperties
Etidronate disodium
7414-83-7
Thumb
  • InChI Key: GWBBVOVXJZATQQ-UHFFFAOYSA-L
  • Monoisotopic Mass: 249.93841492
  • Average Mass: 249.9919
DBSALT000842
Categories
UNIIM16PXG993G
CAS number2809-21-4
WeightAverage: 206.0282
Monoisotopic: 205.974525634
Chemical FormulaC2H8O7P2
InChI KeyDBVJJBKOTRCVKF-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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganophosphorus compounds
ClassOrganic phosphonic acids and derivatives
Sub ClassBisphosphonates
Direct ParentBisphosphonates
Alternative Parents
Substituents
  • Bisphosphonate
  • Organophosphonic acid
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Pharmacology
IndicationFor 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.
PharmacodynamicsEtidronic 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 actionBisphosphonates, 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.
Related Articles
AbsorptionThe amount of drug absorbed after an oral dose is approximately 3%.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Not metabolized.

Route of eliminationEtidronate 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 lifeIn normal subjects, plasma half-life of etidronic acid, based on non-compartmental pharmacokinetics is 1 to 6 hours.
ClearanceNot Available
ToxicityClinical 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral
Tabletoral400 mg
Kit; tabletoral
Solutionintravenous50 mg
Tabletoral200 mg/1
Tabletoral400 mg/1
Tabletoral200 mg
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.
PatentsNot Available
Properties
StateSolid
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-2ChemAxon
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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
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 ReferencesNot Available
External Links
ATC CodesM05BA01M05BB01
AHFS Codes
  • 92:00.00
PDB EntriesNot Available
FDA labelDownload (42 KB)
MSDSDownload (44.4 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

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
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
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 ]
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Drug created on June 13, 2005 07:24 / Updated on May 03, 2016 12:21