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Details

Stereochemistry ACHIRAL
Molecular Formula C3H11NO7P2
Molecular Weight 235.0695
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PAMIDRONIC ACID

SMILES

NCCC(O)(P(O)(O)=O)P(O)(O)=O

InChI

InChIKey=WRUUGTRCQOWXEG-UHFFFAOYSA-N
InChI=1S/C3H11NO7P2/c4-2-1-3(5,12(6,7)8)13(9,10)11/h5H,1-2,4H2,(H2,6,7,8)(H2,9,10,11)

HIDE SMILES / InChI

Description

Pamidronic acid (Pamidronate Disodium) is a bone resorption inhibitor. The principal pharmacologic action of pamidronate disodium is inhibition of bone resorption. Although the mechanism of antiresorptive action is not completely understood, several factors are thought to contribute to this action. Pamidronate disodium adsorbs to calcium phosphate (hydroxyapatite) crystals in bone and may directly block dissolution of this mineral component of bone. In vitro studies also suggest that inhibition of osteoclast activity contributes to inhibition of bone resorption. In animal studies, at doses recommended for the treatment of hypercalcemia, pamidronate disodium inhibits bone resorption apparently without inhibiting bone formation and mineralization. Of relevance to the treatment of hypercalcemia of malignancy is the finding that pamidronate disodium inhibits the accelerated bone resorption that results from osteoclast hyperactivity induced by various tumors in animal studies. Pamidronate disodium, in conjunction with adequate hydration, is indicated for the treatment of moderate or severe hypercalcemia associated with malignancy, with or without bone metastases. Pamidronate disodium is indicated for the treatment of patients with moderate to severe Paget’s disease of bone. Pamidronate disodium is indicated, in conjunction with standard antineoplastic therapy, for the treatment of osteolytic bone metastases of breast cancer and osteolytic lesions of multiple myeloma.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
55.9 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PAMIDRONATE DISODIUM
Primary
PAMIDRONATE DISODIUM
Primary
PAMIDRONATE DISODIUM

Cmax

ValueDoseCo-administeredAnalytePopulation
1.92 μg/mL
90 mg single, intravenous
PAMIDRONATE DISODIUM plasma
Homo sapiens
0.73 μg/mL
30 mg single, intravenous
PAMIDRONATE DISODIUM plasma
Homo sapiens
1.44 μg/mL
60 mg single, intravenous
PAMIDRONATE DISODIUM plasma
Homo sapiens
2.61 μg/mL
90 mg single, intravenous
PAMIDRONATE DISODIUM plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
10.2 μg × h/mL
90 mg single, intravenous
PAMIDRONATE DISODIUM plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
28 h
30 mg single, intravenous
PAMIDRONATE DISODIUM plasma
Homo sapiens
28 h
60 mg single, intravenous
PAMIDRONATE DISODIUM plasma
Homo sapiens
28 h
90 mg single, intravenous
PAMIDRONATE DISODIUM plasma
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as victim

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
Moderate Hypercalcemia The recommended dose of pamidronate disodium in moderate hypercalcemia (corrected serum calcium* of approximately 12 to 13.5 mg/dL) is 60 to 90 mg given as a SINGLE-DOSE, intravenous infusion over 2 to 24 hours. Longer infusions (i.e., >2 hours) may reduce the risk for renal toxicity, particularly in patients with preexisting renal insufficiency. Severe Hypercalcemia The recommended dose of pamidronate disodium in severe hypercalcemia (corrected serum calcium* >13.5 mg/dL) is 90 mg given as a SINGLE-DOSE, intravenous infusion over 2 to 24 hours. Longer infusions (i.e., >2 hours) may reduce the risk for renal toxicity, particularly in patients with preexisting renal insufficiency.
Route of Administration: Intravenous
In Vitro Use Guide
BMSCs proliferation was significantly inhibited with 10(−4) M Pamidronic acid (pamidronate) after 72h and 168h, and with 6 × 10(−5) M pamidronate after 168h. Alveolar osteoblasts cultured in osteogenic medium exhibited significantly lower alkaline phosphatase (AP) activities with 6 × 10(−5) M and 10(−4) M pamidronate (39% and 16% of the unsupplemented group) as compared to all lower concentration groups after 168h.