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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
SynonymLanguageCode
1-hydroxyethane 1,1-diphosphonic acidNot AvailableNot Available
Acetodiphosphonic acidNot AvailableNot Available
Acide etidroniqueFrenchINN
Acido etidronicoSpanishINN
Acidum etidronicumLatinINN
EHDPNot AvailableNot Available
EtidronateNot AvailableNot Available
EtidronsäureGermanNot Available
HEDPNot AvailableNot Available
Hydroxyethanediphosphonic acidNot AvailableNot Available
Oxyethylidenediphosphonic acidNot AvailableNot Available
Salts
Name/CAS Structure Properties
Etidronate disodium
Thumb
  • InChI Key: GWBBVOVXJZATQQ-UHFFFAOYNA-L
  • Monoisotopic Mass: 249.93841492
  • Average Mass: 249.9919
DBSALT000842
Brand names
NameCompany
DidronelProcter & Gamble
Brand mixtures
Brand NameIngredients
DidrocalEtidronate Disodium + Calcium Carbonate
Categories
CAS number7414-83-7
WeightAverage: 206.0282
Monoisotopic: 205.974525634
Chemical FormulaC2H8O7P2
InChI KeyInChIKey=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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganophosphorus Compounds
ClassOrganic Phosphonic Acids and Derivatives
SubclassOrganic Phosphonic Acids
Direct parentOrganic Phosphonic Acids
Alternative parentsPolyamines
Substituentspolyamine
Classification descriptionThis compound belongs to the organic phosphonic acids. These are organic compounds containing phosphonic acid.
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.
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
Property Value Probability
Human Intestinal Absorption - 0.8918
Blood Brain Barrier + 0.8901
Caco-2 permeable - 0.8581
P-glycoprotein substrate Non-substrate 0.7483
P-glycoprotein inhibitor I Non-inhibitor 0.9639
P-glycoprotein inhibitor II Non-inhibitor 0.9951
Renal organic cation transporter Non-inhibitor 0.9726
CYP450 2C9 substrate Non-substrate 0.7545
CYP450 2D6 substrate Non-substrate 0.8473
CYP450 3A4 substrate Non-substrate 0.6987
CYP450 1A2 substrate Non-inhibitor 0.9061
CYP450 2C9 substrate Non-inhibitor 0.9047
CYP450 2D6 substrate Non-inhibitor 0.9222
CYP450 2C19 substrate Non-inhibitor 0.9186
CYP450 3A4 substrate Non-inhibitor 0.9595
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9873
Ames test Non AMES toxic 0.8875
Carcinogenicity Carcinogens 0.5282
Biodegradation Not ready biodegradable 0.7701
Rat acute toxicity 1.9653 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9519
hERG inhibition (predictor II) Non-inhibitor 0.9495
Pharmacoeconomics
Manufacturers
  • Mgi pharma inc
  • Procter and gamble pharmaceuticals inc sub procter and gamble co
  • Mylan pharmaceuticals inc
  • Ge healthcare
  • Mallinckrodt inc
Packagers
Dosage forms
FormRouteStrength
TabletOral200 mg
TabletOral400 mg
Prices
Unit descriptionCostUnit
Didronel 400 mg tablet8.31USDtablet
Didronel 200 mg tablet4.16USDtablet
Co Etidronate 200 mg Tablet0.86USDtablet
Mylan-Etidronate 200 mg Tablet0.86USDtablet
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 solubility1.15e+01 g/lALOGPS
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 area135.29ChemAxon
rotatable bond count2ChemAxon
refractivity34.51ChemAxon
polarizability13.97ChemAxon
number of rings0ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00314
KEGG CompoundC07736
PubChem Compound3305
PubChem Substance46507694
ChemSpider3189
BindingDB50115102
ChEBI4907
ChEMBLCHEMBL871
Therapeutic Targets DatabaseDNC000629
PharmGKBPA449548
Drug Product Database2248686
RxListhttp://www.rxlist.com/cgi/generic/didronel.htm
WikipediaEtidronic_acid
ATC CodesM05BA01M05BB01
AHFS Codes
  • 92:00.00
PDB EntriesNot Available
FDA labelshow(42 KB)
MSDSshow(44.4 KB)
Interactions
Drug Interactions
Drug
AluminiumFormation of non-absorbable complexes
CalciumFormation of non-absorbable complexes
Calcium AcetateCalcium Salts may decrease the serum concentration of Bisphosphonate Derivatives such as etidronic acid (etidronate). Avoid administration of oral calcium supplements within 2 hours before or after tiludronate/clodronate/etidronate.
Calcium ChlorideCalcium salts may decrease the serum concentration of bisphosphonate derivatives. Avoid administration of oral calcium supplements within 2 hours before or after tiludronate/clodronate/etidronate.
IronFormation of non-absorbable complexes
Iron DextranFormation of non-absorbable complexes
MagnesiumFormation of non-absorbable complexes
Magnesium oxideFormation of non-absorbable complexes
SucralfateFormation of non-absorbable complexes
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.

1. Hydroxylapatite

Kind: small molecule

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details

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
  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
  3. Ono K, Wada S: [Regulation of calcification by bisphosphonates] Clin Calcium. 2004 Jun;14(6):60-3. Pubmed
  4. Takaishi Y: [Treatment of periodontal disease, prevention and bisphosphonate] Clin Calcium. 2003 Feb;13(2):173-6. Pubmed

2. Receptor-type tyrosine-protein phosphatase S

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Receptor-type tyrosine-protein phosphatase S Q13332 Details

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
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. V-type proton ATPase catalytic subunit A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
V-type proton ATPase catalytic subunit A P38606 Details

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

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13