etidronic acid

Small moleculeapproved

Approved

Sep 28, 1973

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. — NCATS

Clinical trial activity

5 trials · 9 clinical orgs · 6 marketing orgs

Phase 1

Phase 2

Phase 3

Phase 4

Earliest trial started Aug 1, 1992 (NCT00376662)

Timeline

1970s

Sep 28, 1973
Mallinckrodt — Earliest FDA Approval
Sep 28, 1973
Mallinckrodt — NDA Secondary Org
Sep 28, 1973
Mallinckrodt — NDA Organization
Nov 18, 1976
General Electric — NDA Secondary Org
Sep 1, 1977
Allergan — NDA Secondary Org

1980s

Apr 20, 1987
MGI Pharma — NDA Secondary Org

2000s

Jan 1, 2001
Earliest Phase 1 Sponsor(trial)
Jan 24, 2003
Mylan — Marketing Organization
Jan 24, 2003
PHARMOBEDIENT — Marketing Organization
Jan 1, 2009
Earliest Phase 3 Sponsor(trial)

Indications

Approved for

Studied for

Mechanism of action

ATPINHIBITOR
ATP inhibitor
1st generation of biphosphonates, moa: its incorporated in ATP anologues, which accumulate in osteoclasts leading to its early apoptosis (specific to osteoclast, because it binds to hydropatite, and is then slowly released when the bone is reabsorded)

Approval history

approvedPriority reviewSep 28, 1973

Chemistry & pharmacology

Loading structure…

SMILES

CC(O)(P(=O)(O)O)P(=O)(O)O

Mol. weight: 206.03 g/mol
Lipinski Ro5: Pass
Rule of 3: No
Chirality: Achiral Molecule
Inorganic: No
Polymer: No
Delivery: Oral, Parenteral
Availability: Discontinued

Oral

Yes

Parenteral

Yes

Topical

Sources

Also known as

1,1,1-ethanetriol diphosphonate
1,1,1-ethanetriol diphosphonate
1-hydroxy-1,1-diphosphonoethane
1-hydroxy-1,1-diphosphonoethane
1-hydroxyethane-1,1-bisphosphonic acid
1-hydroxyethane-1,1-bisphosphonic acid
1-hydroxyethane-1,1-diphosphonate
1-hydroxyethane-1,1-diphosphonate
1-hydroxyethane 1,1-diphosphonic acid
1-hydroxyethane 1,1-diphosphonic acid
1-hydroxyethane-1,1-diphosphonic acid
1-hydroxyethane-1,1-diphosphonic acid
1-hydroxyethanediphosphonic acid
1-hydroxyethanediphosphonic acid
(1-hydroxyethylene)diphosphonic acid
(1-hydroxyethylene)diphosphonic acid
1-hydroxyethylidene-1,1-bisphosphonate
1-hydroxyethylidene-1,1-bisphosphonate
1-hydroxyethylidene-1,1-diphosphonic acid
1-hydroxyethylidene-1,1-diphosphonic acid
(1-hydroxyethylidene)bis(phosphonic acid)
(1-hydroxyethylidene)bis(phosphonic acid)
(1-hydroxyethylidene)bisphosphonic acid
(1-hydroxyethylidene)bisphosphonic acid
(1-hydroxy-ethylidene)diphosphonic acid
(1-hydroxy-ethylidene)diphosphonic acid
(1-hydroxyethylidene)diphosphonic acid
(1-hydroxyethylidene)diphosphonic acid
acetodiphosphonic acid
acetodiphosphonic acid
acide étidronique
acide étidronique
ácido etidrónico
ácido etidrónico
acidum etidronicum
acidum etidronicum
cintichem technetium 99m hedspa
cintichem technetium 99m hedspa
didronel
didronel
didronel
didronel iv
didronel iv
didronel pmo
ehdp
ehdp
ethane-1-hydroxy-1,1-bisphosphonic acid
ethane-1-hydroxy-1,1-bisphosphonic acid
ethane-1-hydroxy-1,1-diphosphonate
ethane-1-hydroxy-1,1-diphosphonate
ethane-1-hydroxy-1,1-diphosphonic acid
ethane-1-hydroxy-1,1-diphosphonic acid
ethidronate
ethidronate
ethidronate
ethydronate
etidronate
etidronate
etidronate
etidronate
etidronate
etidronate
etidronate disodium
etidronate disodium
etidronate disodium
etidronate disodium
etidronic acid
etidronic acid
etidronic acid
etidronic acid
etidronic acid
etidronic acid
etidronic acid
etidronic acid
etidronic acid
etidronsäure
etidronsäure
hedp
hedp
hydroxyethanediphosphonic acid
hydroxyethanediphosphonic acid
hydroxyethanediphosphonic acid
(hydroxyethylidene)diphosphonic acid
(hydroxyethylidene)diphosphonic acid
mpi stannous diphosphonate
mpi stannous diphosphonate
osteoscan
osteoscan
osteoscan
osteoscan
oxyethylidenediphosphonic acid
oxyethylidenediphosphonic acid
oxyethylidenediphosphonic acid
tc-99m-hdp
tc-99m-hmdp
tc-99m hydroxymethylene diphosphonate
tc-99m-oxidronate
technetium hmdp
technetium osteoscan-hdp
technetium salt (hydroxymethylene)bis(phosphonic acid)
technetium tc 99m diphosphonate-tin kit
technetium tc 99m diphosphonate-tin kit
technetium tc 99m etidronate
technetium tc 99m etidronate
technetium tc-99m etidronate kit
technetium tc-99m etidronate kit
technetium tc-99m etidronate kit
technetium tc-99m etidronate kit
technetium tc 99m hydroxymethylene diphosphonate

Clinical trials

NCT ID	Phase	Start date	Sponsor(s)
NCT05778227	N/A	Nov 16, 2021	Dow University of Health Sciences
NCT01585402	Phase 1	Apr 9, 2012	National Heart, Lung, and Blood Institute (NHLBI)
NCT01048463	Phase 3	Dec 1, 2009	Sun Yat-Sen University
NCT00311571	Phase 1	Aug 1, 2001	Centre National d'Etudes Spatiales, European Space Agency, MEDES-IMPS, National Space Development Agency, Japan
NCT00376662	Phase 4	Aug 1, 1992	British Thoracic Society, Newcastle University

Showing 5 of 5 trials

Page 1 / 1

Organizations

Research & Development (9)

Organization	Org type	Trials	As lead sponsor	Phases	Earliest year
British Thoracic Society	Academic/Hospital	1	1	1	1992
Centre National d'Etudes Spatiales	Academic/Hospital	1	1	1	2001
Dow University of Health Sciences	Academic/Hospital	1	1	1	2021
European Space Agency	Academic/Hospital	1	0	1	2001
MEDES-IMPS	Academic/Hospital	1	0	1	2001
National Heart, Lung, and Blood Institute (NHLBI)	Government	1	1	1	2012
National Space Development Agency, Japan	Government	1	0	1	2001
Newcastle University	Academic/Hospital	1	0	1	1992
Sun Yat-Sen University	Academic/Hospital	1	1	1	2009

9 organizations

Page 1 / 1

Marketing (7)

Organization	Org type	Relationship	Date
Allergan	For profit	NDA2	Sep 1, 1977
General Electric	For profit	NDA2	Nov 18, 1976
MGI Pharma	For profit	NDA2	Apr 20, 1987
Mallinckrodt	For profit	NDA2	Sep 28, 1973
Mallinckrodt	For profit	NDA	Sep 28, 1973
Mylan	For profit	MKTG	Jan 24, 2003
PHARMOBEDIENT	For profit	MKTG	Jan 24, 2003