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Details

Stereochemistry ACHIRAL
Molecular Formula C2H4O7P2.4Na
Molecular Weight 293.9556
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ETIDRONATE TETRASODIUM

SMILES

[Na+].[Na+].[Na+].[Na+].CC(O)(P([O-])([O-])=O)P([O-])([O-])=O

InChI

InChIKey=KWXLCDNSEHTOCB-UHFFFAOYSA-J
InChI=1S/C2H8O7P2.4Na/c1-2(3,10(4,5)6)11(7,8)9;;;;/h3H,1H3,(H2,4,5,6)(H2,7,8,9);;;;/q;4*+1/p-4

HIDE SMILES / InChI

Molecular Formula C2H4O7P2
Molecular Weight 201.9965
Charge -4
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Molecular Formula Na
Molecular Weight 22.9898
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Etidronate is a salt of etidronic acid (brand name Didronel, also known as EHDP) a diphosphonate, which is indicated 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. Didronel is not approved for the treatment of osteoporosis. This drugs acts primarily on bone. It can inhibit the formation, growth, and dissolution of hydroxyapatite crystals and their amorphous precursors by chemisorption to calcium phosphate surfaces. Inhibition of crystal resorption occurs at lower doses than are required to inhibit crystal growth. Both effects increase as the dose increases. Preclinical studies indicate etidronate disodium does not cross the blood-brain barrier. Didronel is not metabolized. The amount of drug absorbed after an oral dose is approximately 3 percent. 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 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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: CHEMBL2366048
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DIDRONEL

Approved Use

Didronel is indicated 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. Didronel is not approved for the treatment of osteoporosis. Paget’s Disease: Didronel is indicated for the treatment of symptomatic Paget's disease of bone. Didronel therapy usually arrests or significantly impedes the disease process as evidenced by: --Symptomatic relief, including decreased pain and/or increased mobility (experienced by 3 out of 5 patients). --Reductions in serum alkaline phosphatase and urinary hydroxyproline levels (30 percent or more in 4 out of 5 patients). --Histomorphometry showing reduced numbers of osteoclasts and osteoblasts, and more lamellar bone formation. Bone scans showing reduced radionuclide uptake at pagetic lesions. In addition, reductions in pagetically elevated cardiac output and skin temperature have been observed in some patients. In many patients, the disease process will be suppressed for a period of at least 1 year following cessation of therapy. The upper limit of this period has not been determined. The effects of the Didronel treatment in patients with asymptomatic Paget's disease have not been studied. However, Didronel treatment of such patients may be warranted if extensive involvement threatens irreversible neurologic damage, major joints, or major weight-bearing bones. Heterotopic Ossification: Didronel is indicated in the prevention and treatment of heterotopic ossification following total hip replacement or due to spinal cord injury. Didronel reduces the incidence of clinically important heterotopic bone by about two-thirds. Among those patients who form heterotopic bone, Didronel retards the progression of immature lesions and reduces the severity by at least half. Follow-up data (at least 9 months posttherapy) suggest these benefits persist. In total hip replacement patients, Didronel does not promote loosening of the prosthesis or impede trochanteric reattachment. In spinal cord injury patients, Didronel does not inhibit fracture healing or stabilization of the spine.

Launch Date

1977
Preventing
DIDRONEL

Approved Use

Didronel is indicated 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. Didronel is not approved for the treatment of osteoporosis. Paget’s Disease: Didronel is indicated for the treatment of symptomatic Paget's disease of bone. Didronel therapy usually arrests or significantly impedes the disease process as evidenced by: --Symptomatic relief, including decreased pain and/or increased mobility (experienced by 3 out of 5 patients). --Reductions in serum alkaline phosphatase and urinary hydroxyproline levels (30 percent or more in 4 out of 5 patients). --Histomorphometry showing reduced numbers of osteoclasts and osteoblasts, and more lamellar bone formation. Bone scans showing reduced radionuclide uptake at pagetic lesions. In addition, reductions in pagetically elevated cardiac output and skin temperature have been observed in some patients. In many patients, the disease process will be suppressed for a period of at least 1 year following cessation of therapy. The upper limit of this period has not been determined. The effects of the Didronel treatment in patients with asymptomatic Paget's disease have not been studied. However, Didronel treatment of such patients may be warranted if extensive involvement threatens irreversible neurologic damage, major joints, or major weight-bearing bones. Heterotopic Ossification: Didronel is indicated in the prevention and treatment of heterotopic ossification following total hip replacement or due to spinal cord injury. Didronel reduces the incidence of clinically important heterotopic bone by about two-thirds. Among those patients who form heterotopic bone, Didronel retards the progression of immature lesions and reduces the severity by at least half. Follow-up data (at least 9 months posttherapy) suggest these benefits persist. In total hip replacement patients, Didronel does not promote loosening of the prosthesis or impede trochanteric reattachment. In spinal cord injury patients, Didronel does not inhibit fracture healing or stabilization of the spine.

Launch Date

1977
PubMed

PubMed

TitleDatePubMed
Possibility of "distraction arthrogenesis": first report in rabbit model.
2001
Effect of menatetrenone on bone mineral density and incidence of vertebral fractures in postmenopausal women with osteoporosis: a comparison with the effect of etidronate.
2001
Analgesic effect of etidronate on degenerative joint disease.
2001
Initiation of osteoporosis treatment after bone mineral density testing.
2001
Consensus statement on the modern therapy of Paget's disease of bone from a Western Osteoporosis Alliance symposium. Biannual Foothills Meeting on Osteoporosis, Calgary, Alberta, Canada, September 9-10, 2000.
2001 Apr
Analgesic effect of bisphosphonates in mice.
2001 Apr
186Re-1,4,8,11-tetraaza cyclotetradecyl-1,4,8,11-tetramethylene phosphonic acid: a novel agent for possible use in metastatic bone-pain palliation.
2001 Aug
Inhibition of bone resorption by alendronate and risedronate does not require osteoclast apoptosis.
2001 Dec
[Therapy of osteoporosis. Risk factors alone are not an indication].
2001 Dec 6
Risedronate pharmacokinetics and intra- and inter-subject variability upon single-dose intravenous and oral administration.
2001 Feb
Treatment of osteoporosis with bisphosphonates.
2001 Feb
Skeletal uptake and soft-tissue retention of 186Re-HEDP and 153Sm-EDTMP in patients with metastatic bone disease.
2001 Feb
[Tumor-induced hypercalcemia. Review of bisphosphonate treatment].
2001 Jul
A multicentre observational study of radionuclide therapy in patients with painful bone metastases of prostate cancer.
2001 Jul
Role of bisphosphonates and calcitonin in the prevention and treatment of osteoporosis.
2001 Jul
The use of scintigraphy to demonstrate the rapid esophageal transit of the oval film-coated placebo risedronate tablet compared to a round uncoated placebo tablet when administered with minimal volumes of water.
2001 Jul 17
The in-vitro porcine adhesion model is not predictive of the esophageal transit of risedronate tablets in humans.
2001 Jul 17
Prevalence and determinants of osteoporosis drug prescription among patients with high exposure to glucocorticoid drugs.
2001 Jun
Re: Lanza et al.--Endoscopic comparison of alendronate and risedronate.
2001 Jun
186Re-etidronate. Efficacy of palliative radionuclide therapy for painful bone metastases.
2001 Mar
Radionuclide therapy for painful bone metastases. An Italian multicentre observational study. Writing Committee of an Ad Hoc Study Group.
2001 Mar
Prevention of corticosteroid induced osteoporosis in inpatients recently discharged from a tertiary teaching hospital.
2001 Mar
Protective effect of short-tem calcitriol or cyclical etidronate on bone loss after cardiac or lung transplantation.
2001 Mar
Prevention and treatment of osteoporosis.
2001 Mar-Apr
[The development of new drugs for osteoporosis in Japan].
2001 May
Risedronate: clinical usage.
2001 May
Bisphosphonates alendronate and ibandronate inhibit artery calcification at doses comparable to those that inhibit bone resorption.
2001 May
Effect of combined risedronate and hormone replacement therapies on bone mineral density in postmenopausal women.
2001 May
The role of combination treatment for osteoporosis.
2001 May
[Therapy of osteoporosis from the viewpoint of evidence-based medicine].
2001 May 15
[Alternatives to hormonal treatment for the prevention of postmenopausal osteoporosis: the bisphosphonates].
2001 Nov
Bisphosphonate treatment suppresses not only stochastic remodeling but also the targeted repair of microdamage.
2001 Nov
Role of alendronate and risedronate in preventing and treating osteoporosis.
2001 Nov
Rhenium-188 HEDP to treat painful bone metastases.
2001 Nov
Conventional treatment of hypercalcemia of malignancy.
2001 Nov 15
Advances in the biology and treatment of myeloma bone disease.
2001 Nov 15
A method to assess the proportion of treatment effect explained by a surrogate endpoint.
2001 Nov 15
[Economic aspects of osteoporosis therapy. What does a prevented fracture cost?].
2001 Nov 22
Risedronate treatment and extended fracture protection in postmenopausal women.
2001 Nov-Dec
Risedronate increases bone density and reduces vertebral fracture risk within one year in men on corticosteroid therapy.
2001 Oct
Alendronate for the treatment of osteoporosis in men.
2001 Oct
Comparative efficacy and safety study of etidronate and alendronate in postmenopausal osteoporosis. effect of adding hormone replacement therapy.
2001 Oct
Maintenance of cancellous bone in ovariectomized, human parathyroid hormone [hPTH(1-84)]-treated rats by estrogen, risedronate, or reduced hPTH.
2001 Oct
Nitrogen-containing bisphosphonates induce apoptosis of Caco-2 cells in vitro by inhibiting the mevalonate pathway: a model of bisphosphonate-induced gastrointestinal toxicity.
2001 Oct
[Osteoporosis. Fracture as alarm signal].
2001 Oct 11
Risedronate: a new oral bisphosphonate.
2001 Sep
Pharmacologic therapy for the treatment and prevention of osteoporosis.
2001 Sep
[Optimizing treatment of osteoporosis. Rapidly effective therapy lowers fracture risk in 1 year up to 70%].
2001 Sep 6
Bisphosphonates are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase.
2001 Sep 7
Refractory heterotopic ossification with complications.
2001 Summer
Patents

Patents

Sample Use Guides

should be taken as a single, oral dose. Paget’s Disease: Initial Treatment Regimens: 5 to 10 mg/kg/day, not to exceed 6 months, or 11 to 20 mg/kg/day, not to exceed 3 months. The recommended initial dose is 5 mg/kg/day for a period not to exceed 6 months. Doses above 10 mg/kg/day should be reserved for when 1) lower doses are ineffective or 2) there is an overriding need to suppress rapid bone turnover (especially when irreversible neurologic damage is possible) or reduce elevated cardiac output. Doses in excess of 20 mg/kg/day are not recommended.
Route of Administration: Oral
In vitro cytotoxicity of etidronic acid to MCF-7 cells was estimated on the basis of clonogenicity assays, while cell cycle effects were determined by using flow cytometry. A 24-hour treatment with etidronic acid (10 mM) with or without strontium chloride was cytototoxic to MCF-7cells. Etidronic acid (1, 10 mM) caused a decrease in the S-phase population and an increase in the G2/M population. Treatment of MCF-7 human breast cancer cells with etidronic acid (10 mM) for six hours caused mutations in exons 6 and 8 of the p53 gene in MCF-7 cells.
Substance Class Chemical
Created
by admin
on Sat Dec 16 04:54:50 GMT 2023
Edited
by admin
on Sat Dec 16 04:54:50 GMT 2023
Record UNII
CZZ9T1T1X4
Record Status Validated (UNII)
Record Version
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Name Type Language
ETIDRONATE TETRASODIUM
WHO-DD  
Common Name English
TETRASODIUM ETIDRONATE [INCI]
Common Name English
TETRASODIUM ETIDRONATE
INCI  
INCI  
Official Name English
Etidronate tetrasodium [WHO-DD]
Common Name English
PHOSPHONIC ACID, (1-HYDROXYETHYLIDENE)BIS-, TETRASODIUM SALT
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C443
Created by admin on Sat Dec 16 04:54:50 GMT 2023 , Edited by admin on Sat Dec 16 04:54:50 GMT 2023
NCI_THESAURUS C67439
Created by admin on Sat Dec 16 04:54:50 GMT 2023 , Edited by admin on Sat Dec 16 04:54:50 GMT 2023
Code System Code Type Description
CAS
29329-71-3
Created by admin on Sat Dec 16 04:54:50 GMT 2023 , Edited by admin on Sat Dec 16 04:54:50 GMT 2023
NON-SPECIFIC STOICHIOMETRY
FDA UNII
CZZ9T1T1X4
Created by admin on Sat Dec 16 04:54:50 GMT 2023 , Edited by admin on Sat Dec 16 04:54:50 GMT 2023
PRIMARY
RXCUI
1364894
Created by admin on Sat Dec 16 04:54:50 GMT 2023 , Edited by admin on Sat Dec 16 04:54:50 GMT 2023
PRIMARY RxNorm
NCI_THESAURUS
C97315
Created by admin on Sat Dec 16 04:54:50 GMT 2023 , Edited by admin on Sat Dec 16 04:54:50 GMT 2023
PRIMARY
EPA CompTox
DTXSID7029663
Created by admin on Sat Dec 16 04:54:50 GMT 2023 , Edited by admin on Sat Dec 16 04:54:50 GMT 2023
PRIMARY
DAILYMED
CZZ9T1T1X4
Created by admin on Sat Dec 16 04:54:50 GMT 2023 , Edited by admin on Sat Dec 16 04:54:50 GMT 2023
PRIMARY
PUBCHEM
19629
Created by admin on Sat Dec 16 04:54:50 GMT 2023 , Edited by admin on Sat Dec 16 04:54:50 GMT 2023
PRIMARY
ECHA (EC/EINECS)
223-267-7
Created by admin on Sat Dec 16 04:54:50 GMT 2023 , Edited by admin on Sat Dec 16 04:54:50 GMT 2023
PRIMARY
CAS
3794-83-0
Created by admin on Sat Dec 16 04:54:50 GMT 2023 , Edited by admin on Sat Dec 16 04:54:50 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE