DT-Web

DB01077 - Etidronic acid


Identification
Name Etidronic acid
Accession Number DB01077 (APRD00964)
Type small molecule
Description A diphosphonate which affects calcium metabolism. It inhibits ectopic calcification and slows down bone resorption and bone turnover. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 206.0282
Groups approved
Monoisotopic Weight 205.974525634
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.
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.
Absorption The amount of drug absorbed after an oral dose is approximately 3%.
Protein binding Not Available
Biotransformation 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.
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
Interactions
Drug Interactions
Drug Mechanism of interaction
Aluminium Formation of non-absorbable complexes
Calcium Formation of non-absorbable complexes
Calcium Acetate Calcium 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 Chloride Calcium salts may decrease the serum concentration of bisphosphonate derivatives. Avoid administration of oral calcium supplements within 2 hours before or after tiludronate/clodronate/etidronate.
Iron Formation of non-absorbable complexes
Iron Dextran Formation of non-absorbable complexes
Magnesium Formation of non-absorbable complexes
Magnesium oxide Formation of non-absorbable complexes
Sucralfate Formation 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.

Targets


Hydroxyapatite
Name Hydroxyapatite
Gene Name Not Available
Pharmacological action yes
Actions antagonist
References
  • 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
  • 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
  • Ono K, Wada S: [Regulation of calcification by bisphosphonates] Clin Calcium. 2004 Jun;14(6):60-3. - Pubmed
  • Takaishi Y: [Treatment of periodontal disease, prevention and bisphosphonate] Clin Calcium. 2003 Feb;13(2):173-6. - Pubmed
DTHybrid score Not Available
Receptor-type tyrosine-protein phosphatase S
Name Receptor-type tyrosine-protein phosphatase S
Gene Name PTPRS
Pharmacological action unknown
Actions inhibitor
References
  • 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
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.9359
V-type proton ATPase catalytic subunit A
Name V-type proton ATPase catalytic subunit A
Gene Name ATP6V1A
Pharmacological action unknown
Actions inhibitor
References
  • 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
DTHybrid score 1.6879

Predictions


Id Partner name Gene Name Score
6056 Receptor-type tyrosine-protein phosphatase epsilon PTPRE 0.2732
1376 Tyrosine-protein phosphatase non-receptor type 4 PTPN4 0.2728
853 Farnesyl pyrophosphate synthetase FDPS 0.1377
687 Tyrosine-protein phosphatase non-receptor type 1 PTPN1 0.0812
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