Pamidronic acid

Absorption

In patients with a creatinine clearance >90mL/min, a 90mg intravenous dose reached a Cmax of 1.92±1.08μg/mL, with a Tmax of 4h, and an AUC of 10.2±6.95μg*h/mL.
In patients with a creatinine clearance 61-90mL/min, a 90mg intravenous dose reached a Cmax of 1.86±0.50μg/mL, with a Tmax of 4h, and an AUC of 10.7—3.91μg*h/mL.[A203264
In patients with a creatinine clearance 30-60mL/min, a 90mg intravenous dose reached a Cmax of 1.84±0.58μg/mL, with a Tmax of 4h, and an AUC of 10.1±3.38μg*h/mL.
In patients with a creatinine clearance <30mL/min, a 90mg intravenous dose reached a Cmax of 1.93±0.53μg/mL, with a Tmax of 4h, and an AUC of 34.0±8.37μg*h/mL.

Toxicity

Patients experiencing and overdose may present with hypocalcemia, fever, hypotension, and taste perversion. Overdose can be managed by symptomatic and supportive treatment which may include the administration of steroids and intravenous calcium.

Chemical properties

White Solid

Originator

Aredia,Novartis,India

The Uses of Pamidronic acid

anticancer

The Uses of Pamidronic acid

A biphosphonate bone resorption inhibitor.

Background

Pamidronic acid is a second generation, nitrogen containing bisphosphonate similar to neridronic acid and alendronic acid. Pamidronic acid was first described in the literature in 1977. The second generation bisphosphonates are less common as third generation bisphosphonates, such as ibandronic acid, zoledronic acid, minodronic acid, and risedronic acid are becoming more popular.
Pamidronic acid was granted FDA approval on 31 October 1991.

Indications

Pamidronate is indicated to treat moderate to severe hypercalcemia of malignancy, moderate to severe Paget's disease of bone, osteolytic bone metastases of breast cancer, and osteolytic lesions of multiple myeloma.

What are the applications of Application

Pamidronic acid is A biphosphonate bone resorption inhibitor.

Definition

ChEBI: Pamidronate is a phosphonoacetic acid.

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

Rescriptor (Agouron).

Therapeutic Function

Bone resorption suppressant

Pharmacokinetics

Pamidronic acid is a second generation, nitrogen containing bisphosphonate that inhibits osteoclast mediated bone loss It has a wide therapeutic index and a long duration of action as it can be given every 3-4 weeks for certain indications. Patients should be counselled regarding the risk of elevated blood urea nitrogen, renal tubular necrosis, and nephrotoxicity.

Metabolism

Pamidronate is not metabolized in vivo.