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Details

Stereochemistry ACHIRAL
Molecular Formula C3H9NO7P2.2Na
Molecular Weight 279.0331
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PAMIDRONATE DISODIUM ANHYDROUS

SMILES

[Na+].[Na+].NCCC(O)(P(O)([O-])=O)P(O)([O-])=O

InChI

InChIKey=CEYUIFJWVHOCPP-UHFFFAOYSA-L
InChI=1S/C3H11NO7P2.2Na/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);;/q;2*+1/p-2

HIDE SMILES / InChI

Molecular Formula C3H9NO7P2
Molecular Weight 233.0536
Charge -2
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Molecular Formula Na
Molecular Weight 22.9898
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PAMIDRONATE DISODIUM

Approved Use

Hypercalcemia of Malignancy 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. Patients who have either epidermoid or non-epidermoid tumors respond to treatment with pamidronate disodium. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated adequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia. The safety and efficacy of pamidronate disodium in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established. Paget’s Disease Pamidronate disodium is indicated for the treatment of patients with moderate to severe Paget’s disease of bone. The effectiveness of pamidronate disodium was demonstrated primarily in patients with serum alkaline phosphatase ≥3 times the upper limit of normal. Pamidronate disodium therapy in patients with Paget’s disease has been effective in reducing serum alkaline phosphatase and urinary hydroxyproline levels by ≥50% in at least 50% of patients, and by ≥30% in at least 80% of patients. Pamidronate disodium therapy has also been effective in reducing these biochemical markers in patients with Paget’s disease who failed to respond, or no longer responded to other treatments. Osteolytic Bone Metastases of Breast Cancer and Osteolytic Lesions of Multiple Myeloma 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. The pamidronate disodium treatment effect appeared to be smaller in the study of breast cancer patients receiving hormonal therapy than in the study of those receiving chemotherapy, however, overall evidence of clinical benefit has been demonstrated.

Launch Date

1991
Primary
PAMIDRONATE DISODIUM

Approved Use

Hypercalcemia of Malignancy 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. Patients who have either epidermoid or non-epidermoid tumors respond to treatment with pamidronate disodium. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated adequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia. The safety and efficacy of pamidronate disodium in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established. Paget’s Disease Pamidronate disodium is indicated for the treatment of patients with moderate to severe Paget’s disease of bone. The effectiveness of pamidronate disodium was demonstrated primarily in patients with serum alkaline phosphatase ≥3 times the upper limit of normal. Pamidronate disodium therapy in patients with Paget’s disease has been effective in reducing serum alkaline phosphatase and urinary hydroxyproline levels by ≥50% in at least 50% of patients, and by ≥30% in at least 80% of patients. Pamidronate disodium therapy has also been effective in reducing these biochemical markers in patients with Paget’s disease who failed to respond, or no longer responded to other treatments. Osteolytic Bone Metastases of Breast Cancer and Osteolytic Lesions of Multiple Myeloma 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. The pamidronate disodium treatment effect appeared to be smaller in the study of breast cancer patients receiving hormonal therapy than in the study of those receiving chemotherapy, however, overall evidence of clinical benefit has been demonstrated.

Launch Date

1991
Primary
PAMIDRONATE DISODIUM

Approved Use

Hypercalcemia of Malignancy 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. Patients who have either epidermoid or non-epidermoid tumors respond to treatment with pamidronate disodium. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated adequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia. The safety and efficacy of pamidronate disodium in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established. Paget’s Disease Pamidronate disodium is indicated for the treatment of patients with moderate to severe Paget’s disease of bone. The effectiveness of pamidronate disodium was demonstrated primarily in patients with serum alkaline phosphatase ≥3 times the upper limit of normal. Pamidronate disodium therapy in patients with Paget’s disease has been effective in reducing serum alkaline phosphatase and urinary hydroxyproline levels by ≥50% in at least 50% of patients, and by ≥30% in at least 80% of patients. Pamidronate disodium therapy has also been effective in reducing these biochemical markers in patients with Paget’s disease who failed to respond, or no longer responded to other treatments. Osteolytic Bone Metastases of Breast Cancer and Osteolytic Lesions of Multiple Myeloma 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. The pamidronate disodium treatment effect appeared to be smaller in the study of breast cancer patients receiving hormonal therapy than in the study of those receiving chemotherapy, however, overall evidence of clinical benefit has been demonstrated.

Launch Date

1991
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.92 μg/mL
90 mg single, intravenous
dose: 90 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PAMIDRONATE DISODIUM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1.44 μg/mL
60 mg single, intravenous
dose: 60 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PAMIDRONATE DISODIUM unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2.61 μg/mL
90 mg single, intravenous
dose: 90 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PAMIDRONATE DISODIUM unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
0.73 μg/mL
30 mg single, intravenous
dose: 30 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PAMIDRONATE DISODIUM unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
10.2 μg × h/mL
90 mg single, intravenous
dose: 90 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PAMIDRONATE DISODIUM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
28 h
60 mg single, intravenous
dose: 60 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PAMIDRONATE DISODIUM unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
28 h
90 mg single, intravenous
dose: 90 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PAMIDRONATE DISODIUM unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
28 h
30 mg single, intravenous
dose: 30 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PAMIDRONATE DISODIUM unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
5.6 mg/kg 3 times / day multiple, oral
Highest studied dose
Dose: 5.6 mg/kg, 3 times / day
Route: oral
Route: multiple
Dose: 5.6 mg/kg, 3 times / day
Sources:
unhealthy, adult
n = 9
Health Status: unhealthy
Condition: hypercalcemia
Age Group: adult
Sex: M+F
Population Size: 9
Sources:
Disc. AE: Diarrhea...
AEs leading to
discontinuation/dose reduction:
Diarrhea
Sources:
120 mg/kg 1 times / day multiple, intravenous
Overdose
Dose: 120 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 120 mg/kg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: hypercalcemia
Age Group: adult
Sources:
Disc. AE: Hypocalcemia...
AEs leading to
discontinuation/dose reduction:
Hypocalcemia
Sources:
285 mg/kg 1 times / day multiple, intravenous
Overdose
Dose: 285 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 285 mg/kg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: hypercalcemia
Age Group: adult
Sex: F
Sources:
Disc. AE: Fever, Hypotension...
AEs leading to
discontinuation/dose reduction:
Fever
Hypotension
Taste perversion
Sources:
90 mg/kg 1 times / day single, intravenous
Recommended
Dose: 90 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 90 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 182
Health Status: unhealthy
Condition: hypercalcemia
Age Group: adult
Sex: M+F
Population Size: 182
Sources:
Disc. AE: Interstitial pneumonitis, Hypocalcemia...
AEs leading to
discontinuation/dose reduction:
Interstitial pneumonitis
Hypocalcemia
Bone pain
Sources:
AEs

AEs

AESignificanceDosePopulation
Diarrhea Disc. AE
5.6 mg/kg 3 times / day multiple, oral
Highest studied dose
Dose: 5.6 mg/kg, 3 times / day
Route: oral
Route: multiple
Dose: 5.6 mg/kg, 3 times / day
Sources:
unhealthy, adult
n = 9
Health Status: unhealthy
Condition: hypercalcemia
Age Group: adult
Sex: M+F
Population Size: 9
Sources:
Hypocalcemia Disc. AE
120 mg/kg 1 times / day multiple, intravenous
Overdose
Dose: 120 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 120 mg/kg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: hypercalcemia
Age Group: adult
Sources:
Fever Disc. AE
285 mg/kg 1 times / day multiple, intravenous
Overdose
Dose: 285 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 285 mg/kg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: hypercalcemia
Age Group: adult
Sex: F
Sources:
Hypotension Disc. AE
285 mg/kg 1 times / day multiple, intravenous
Overdose
Dose: 285 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 285 mg/kg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: hypercalcemia
Age Group: adult
Sex: F
Sources:
Taste perversion Disc. AE
285 mg/kg 1 times / day multiple, intravenous
Overdose
Dose: 285 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 285 mg/kg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: hypercalcemia
Age Group: adult
Sex: F
Sources:
Bone pain Disc. AE
90 mg/kg 1 times / day single, intravenous
Recommended
Dose: 90 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 90 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 182
Health Status: unhealthy
Condition: hypercalcemia
Age Group: adult
Sex: M+F
Population Size: 182
Sources:
Hypocalcemia Disc. AE
90 mg/kg 1 times / day single, intravenous
Recommended
Dose: 90 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 90 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 182
Health Status: unhealthy
Condition: hypercalcemia
Age Group: adult
Sex: M+F
Population Size: 182
Sources:
Interstitial pneumonitis Disc. AE
90 mg/kg 1 times / day single, intravenous
Recommended
Dose: 90 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 90 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 182
Health Status: unhealthy
Condition: hypercalcemia
Age Group: adult
Sex: M+F
Population Size: 182
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​Drug as victim
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Intravenous pamidronate as treatment for osteoporosis after heart transplantation: a prospective study.
2001
[Bone scintigraphy in the control of bone metastasis of breast cancer during pamidronate and tamoxifen combination therapy].
2001 Apr
Intravenous bisphosphonate for hypercalcemia accompanying subcutaneous fat necrosis: a novel treatment approach.
2001 Apr
Analgesic effect of bisphosphonates in mice.
2001 Apr
Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases.
2001 Apr 1
Pamidronate-related nephrotoxicity (tubulointerstitial nephritis) in a patient with osteolytic bone metastases.
2001 Dec
Inhibition of cholesteatomatous bone resorption with pamidronate disodium.
2001 Jan
Clinical and radiological amelioration of refractory peripheral spondyloarthritis by pulse intravenous pamidronate therapy.
2001 Jan
Bisphosphonate therapy in fibrous dysplasia.
2001 Jan
Influence of cyclic intravenous pamidronate on proinflammatory monocytic cytokine profiles and bone density in rheumatoid arthritis treated with low dose prednisolone and methotrexate.
2001 Jan-Feb
Pamidronate decreases tumor-induced osteoclastogenesis in osteopetrotic mice.
2001 Jul
[Chronic recurrent multifocal osteomyelitis in children: report of 17 cases].
2001 Jun
The sugar absorption test in the evaluation of the gastrointestinal intolerance to bisphosphonates: studies with oral pamidronate.
2001 Jun
Effect of pamidronate in preventing local bone loss after total hip arthroplasty: a randomized, double-blind, controlled trial.
2001 Mar
Efficacy of low dose schedule pamidronate infusion in children with osteogenesis imperfecta.
2001 May
Systemic treatment of metastatic breast cancer.
2001 May
Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro.
2001 May
Trastuzumab and breast cancer.
2001 Sep 27
Bone mineral density response to long-term bisphosphonate therapy in fibrous dysplasia.
2001 Summer
Patents

Patents

Sample Use Guides

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
Curator's Comment: Bone marrow stromal cells were isolated from the marrow aspirates obtained from the long/iliac bones, and cultured in medium supplemented with 1 ng/ml bFGF.
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:09:01 GMT 2023
Edited
by admin
on Fri Dec 15 16:09:01 GMT 2023
Record UNII
C7S8VWP5DH
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PAMIDRONATE DISODIUM ANHYDROUS
Common Name English
PHOSPHONIC ACID, (3-AMINO-1-HYDROXYPROPYLIDENE)BIS-, DISODIUM SALT
Common Name English
PAMIDRONIC ACID DISODIUM SALT [MI]
Common Name English
PAMIDRONIC ACID DISODIUM SALT
MI  
Common Name English
NSC-722600
Code English
DISODIUM DIHYDROGEN (3-AMINO-1-HYDROXYPROPYLIDENE)DIPHOSPHONATE
Systematic Name English
ANHYDROUS PAMIDRONATE DISODIUM
Common Name English
GCP-23339A
Code English
Classification Tree Code System Code
NCI_THESAURUS C443
Created by admin on Fri Dec 15 16:09:01 GMT 2023 , Edited by admin on Fri Dec 15 16:09:01 GMT 2023
NCI_THESAURUS C67439
Created by admin on Fri Dec 15 16:09:01 GMT 2023 , Edited by admin on Fri Dec 15 16:09:01 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C84558
Created by admin on Fri Dec 15 16:09:01 GMT 2023 , Edited by admin on Fri Dec 15 16:09:01 GMT 2023
PRIMARY
ECHA (EC/EINECS)
260-647-1
Created by admin on Fri Dec 15 16:09:01 GMT 2023 , Edited by admin on Fri Dec 15 16:09:01 GMT 2023
PRIMARY
NSC
722600
Created by admin on Fri Dec 15 16:09:01 GMT 2023 , Edited by admin on Fri Dec 15 16:09:01 GMT 2023
PRIMARY
SMS_ID
100000092120
Created by admin on Fri Dec 15 16:09:01 GMT 2023 , Edited by admin on Fri Dec 15 16:09:01 GMT 2023
PRIMARY
PUBCHEM
4673
Created by admin on Fri Dec 15 16:09:01 GMT 2023 , Edited by admin on Fri Dec 15 16:09:01 GMT 2023
PRIMARY
FDA UNII
C7S8VWP5DH
Created by admin on Fri Dec 15 16:09:01 GMT 2023 , Edited by admin on Fri Dec 15 16:09:01 GMT 2023
PRIMARY
CAS
57248-88-1
Created by admin on Fri Dec 15 16:09:01 GMT 2023 , Edited by admin on Fri Dec 15 16:09:01 GMT 2023
PRIMARY
EVMPD
SUB21795
Created by admin on Fri Dec 15 16:09:01 GMT 2023 , Edited by admin on Fri Dec 15 16:09:01 GMT 2023
PRIMARY
EPA CompTox
DTXSID5042667
Created by admin on Fri Dec 15 16:09:01 GMT 2023 , Edited by admin on Fri Dec 15 16:09:01 GMT 2023
PRIMARY
MERCK INDEX
m8374
Created by admin on Fri Dec 15 16:09:01 GMT 2023 , Edited by admin on Fri Dec 15 16:09:01 GMT 2023
PRIMARY Merck Index
Related Record Type Details
PARENT -> SALT/SOLVATE
SOLVATE->ANHYDROUS
Related Record Type Details
ACTIVE MOIETY