Description
Agents in the first generation (e.g., etidronate disodium and tiludronate) that were dosed continuously
produced poorly mineralized bone, because there was no interval for appropriate bone mineralization to
occur. Subsequent studies that used a cyclic dosing schedule (400 mg/day for 2 weeks, followed by 2.5 months
of calcium supplementation only) showed improvement in bone mineralization. Etidronate has been
approved for treatment of Paget's disease of the bone but not for treatment of osteoporosis. Tiludronate
is approximately 10-fold more potent than etidronate and, when given orally for 6 months (200, 400, or 800
mg/day), increases BMD by 2%. No further bone loss was detected in patients 6 months after cessation of
therapy.
Chemical Properties
White Crystalline Solid
Originator
Etidron,Gentili,Italy,1977
Uses
Sequestering and chelating agent; scale and corrosion inhibitor.
Uses
Used as a calcium regulator. A bisphosphonate bone resorptive inhibitor
Uses
Etidronate disodium is a bisphosphonate antiresorptive agent,it is used as a calcium regulator.
Definition
ChEBI: An organic sodium salt resulting from the replacement of two protons from etidronic acid (one from from each of the phosphonic acid groups) by sodium ions.
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
Biochem/physiol Actions
Etidronate helps to guard chronic ocular hypertension prompted retinal oxidative stress. It stimulates the development of retinal ganglion cells through insulin-like growth factor 1 (IGF-1) signaling pathway. It may possess neuroprotective effects in in vivo and in vitro rat model of glaucoma. Etidronate belongs to bisphosphonates.
Safety Profile
Poison by intravenous
and subcutaneous routes. Moderately toxic
by ingestion. An experimental teratogen.
Other experimental reproductive effects.
When heated to decomposition it emits
toxic fumes of POx, and Na2O.
Veterinary Drugs and Treatments
Etidronate is a first generation bisphosphonate that may be useful
for the treatment of severe hypercalcemia associated with neoplastic
disease. Its use in human medicine has been largely replaced
with newer, more potent bisphosphonates that can be dosed less
often or have fewer adverse effects. Etidronate is also indicated in
humans for the treatment of Paget’s disease and heterotopic ossification
(e.g., after total hip replacement).
