Etidronic Acid

Absorption

Etidronic acid has an oral bioavailability of 1-10%. Further data regarding pharmacokinetics of etidronic acid are not readily available.

Toxicity

Patients experiencing an overdose may present with hypocalcemia, vomiting, parasthesia, and diarrhea. Overdose can be treated with symptomatic and supportive treatment that may include management of electrolyte imbalances and intravenous calcium gluconate.

Description

Hydroxyethylidene diphosphonic acid (HEDP) is a new type of chlorine-free electroplating complexing agent. It is used as the main agent for stable water quality in the circulating cooling water system, and plays the role of corrosion and scale inhibition. This product is one of the organic polyphosphonic acid-free water tablet conditioners. There are also some other varieties of such products produced in China, such as aminotrimethylenephosphonic acid (ATMP): [CH2PO(OH)2]3N and ethyl acetate Diaminetetramethylenephosphoric acid (EDTMP) and so on. Organic polyphosphonic acid is a type of water treatment agent developed in the late 1960s and confirmed around the 1970s.

Chemical properties

light beige powder

Originator

Etidron,Gentili,Italy,1977

The Uses of Etidronic Acid

Etidronate (Didronel) is a human protein tyrosine phosphatase inhibitor with IC50 of 0.2 μM.

The Uses of Etidronic Acid

1-Hydroxyethylidenebis(phosphonic acid) acts as human protein tyrosine phosphatase inhibitor. It is also useful for photographic applications. It finds application to strengthen bone, osteoporosis treatment and to treat Paget's disease of bone. In addition, it is used in corrosion inhibition in circulating cool water systems, oil fields and low-pressure boilers with electric power, the chemical industry, metallurgy and fertilizers. It is also utilized for formulating reverse osmosis and thermal desalination anti-scaling agents. Furthermore, it is used in detergents, water treatment, cosmetics and pharmaceuticals.

Indications

Etidronate is indicated to treat Paget's disease of bone, as well as the treatment and prevention of heterotropic ossification after total hip replacement of spinal cord injury.

Background

Etidronic acid is a first generation bisphosphonate similar to clodronic acid and tiludronic acid. These drugs were developed to mimic the action of pyrophosphate, a regulator of calcification and decalcification. Etidronate’s use has decreased over the years in favor of the third generation, nitrogen containing bisphosphonate zoledronic acid, ibandronic acid, minodronic acid, and risedronic acid.
Etidronic acid was granted FDA approval on 1 September 1977.

What are the applications of Application

Etidronic acid is a diphosphonate which affects calcium metabolism

Definition

ChEBI: A 1,1-bis(phosphonic acid) that is (ethane-1,1-diyl)bis(phosphonic acid) having a hydroxy substituent at the 1-position. It inhibits the formation, growth, and dissolution of hydroxyapatite crystals by chemisorption to calcium phosphate surfaces.

Manufacturing Process

Phosphorous acid was premixed with acetic acid to form a 50 wt % solution of phosphorous acid dissolved in acetic acid. The acids were mixed on a molar basis of 1.36:1, acetic acid to phosphorous acid, and this corresponded on a mol percentage basis to 57.6% acetic acid and 42.4% phosphorous acid. Acetic anhydride was continuously metered into a stream of the phosphorous acid-acetic acid mixture to form the reaction solution. The acetic anhydride was metered into the acid mixture at a mol ratio of 1.33 mols of acetic anhydride per mol of phosphorous acid. The metering rates were 18.5 lb/hr of the phosphorous acid/acetic acid premixed solution and 15.1 lb/hr acetic anhydride. The reaction solution was continuously passed through a heat exchanger where it was heated to 190°F then it was continuously fed into a two stage back-mix reaction zone where due to the heat of reaction the temperature rose to 275°F. The average residence in the reaction zone was 27 min. The reaction zone consisted of two back-mix reactors each having a capacity of 7.5 pounds of the reaction solution. A stream of reaction solution was continuously with drawn from the second reactor and continuously mixed with a stream of water which was being metered at a rate of 2 lb/hr. This amount of water corresponded to 18% excess over the theoretical amount necessary to hydrolyze all of the acetyl-containing compounds in the reaction solution to free acids. The hydrolyzed solution was continuously passed through a heat exchanger and cooled to room temperature after which the solution was continuously passed to a crystallizer where, with agitation, the ethane-1-hydroxy-1,1-diphosphonic acid crystallized. The slurry was then filtered and the crystals were recovered and dried. Analysis of the product showed a conversion rate of phosphorous acid to ethane-1-hydroxy-1,1- diphosphonic acid of 86%. Sodium hydroxide may be used to give the disodium salt.

brand name

Didronel (Millot Laboratories, France); Didronel (Procter & Gamble).

Therapeutic Function

Bone calcium regulator

Flammability and Explosibility

Not classified

Pharmacokinetics

Etidronic acid is a first generation bisphosphonate that inhibits the action of osteoclasts, preventing bone resporption. It has a wide therapeutic index as overdoses are not associated with severe toxicity and a long duration of action as it slowly releases from the bone. Patients should be counselled regarding the risk of upper gastrointestinal adverse reactions.

Metabolism

Etidronic acid is not metabolized in vivo