Description
Disodium pamidronate is a calcium metabolism regulator useful in the treatment of
hypercalcemia associated with malignancy. It presumably reduces the bone resorption of
calcium by inhibiting the formation and attachment of osteoclasts. Other potential uses
include osteoporosis and calcitonin-resistant Paget’s disease.
Chemical Properties
White Crystals
Originator
Henkel (United Kingdom)
Uses
A bisphosphonate antiresorptive agent; bone resorption inhibitor.
Uses
A farnesyl diphosphate synthase inhibitor
Uses
Pamidronate disodium is a nitrogen containing bisphosphonate, used to prevent osteoporosis. It is used to prevent bone loss, and treat osteoporosis.
Manufacturing Process
For a batch size of 5 L, 587.5 g (3.2 moles) of mannitol is dissolved in 3.5 L of water. Pamidronic acid (31.6 g, 0.133 moles) is mixed with a 1.0 L aliquot of the mannitol solution to form a slurry. The slurry is then transferred into the remainder of the mannitol solution, and stirred for at least 15 min. Aqueous 1 N sodium hydroxide (270 ml) is then added and the mixture is stirred until a clear, colorless solution results. The pH is then adjusted to 6.50.1 using either 1 M aqueous phosphoric acid or 1 N aqueous sodium hydroxide, as needed. The solution is then filtered through a 0.22 micron filter, and filled at 20°C into vials at 4.0 ml (4.172 g)/vial, under sterile conditions. The aqueous solution is frozen at -37°C and lyophilized (20 mbar, 20°-40°C) to yield 1,250 vials, each containing 30 mg of amorphous disodium pamidronate. The vials are sealed under positive nitrogen pressure. The disodium pamidronate is amorphous (noncrystalline) by X-ray diffraction and contains 0.7 wt-% water.
Brand name
Aredia (Novartis).
Therapeutic Function
Bone resorption suppressant
Biochem/physiol Actions
Pamidronate disodium?has the ability to block Wnt and β-catenin signaling, which modulates the osteogenic differentiation in bone marrow mesenchymal stem cells (BMMSCs). It can also reduce bilirubin-impaired apoptosis and helps to develop dentinogenic dysfunction of stem cells from human deciduous teeth.
Veterinary Drugs and Treatments
Pamidronate may be useful in treating hypercalcemia associated
with vitamin D-related toxicoses or hypercalcemia of malignancy.
There is ongoing research on the use of this drug to determine if
it has clinical usefulness in directly treating “micro-metastases” in
osteosarcomas.