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Details

Stereochemistry ACHIRAL
Molecular Formula C3H10NO7P2.Na
Molecular Weight 257.0513
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PAMIDRONATE MONOSODIUM

SMILES

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

InChI

InChIKey=AFICAMMULQSNNG-UHFFFAOYSA-M
InChI=1S/C3H11NO7P2.Na/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;+1/p-1

HIDE SMILES / InChI
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
[A case of effective bisphosphonate therapy of sequential pamidronate and incadronate for bone metastases from breast cancer].
2000 Aug
Incremental cost analysis of ambulatory clinic and home-based intravenous therapy for patients with multiple myeloma.
2001
[Paget disease or fibrous dysplasia of the radius?--A case report].
2001
Intravenous pamidronate as treatment for osteoporosis after heart transplantation: a prospective study.
2001
Analgesic effect of bisphosphonates in mice.
2001 Apr
Effect of intravenous pamidronate on bone mineral density in adults with cystic fibrosis.
2001 Apr
Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases.
2001 Apr 1
Bisphosphonates regulate cell growth and gene expression in the UMR 106-01 clonal rat osteosarcoma cell line.
2001 Apr 6
Analysis of skeletal-related events in breast cancer and response to therapy.
2001 Aug
Pamidronate-related nephrotoxicity (tubulointerstitial nephritis) in a patient with osteolytic bone metastases.
2001 Dec
Treatment of osteoporosis with bisphosphonates.
2001 Feb
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
Safety and efficacy of bisphosphonates beyond 24 months in cancer patients.
2001 Jul 15
[Analgesic effect of Pamidronate on bone pain in patient with hypertrophic pulmonary osteoarthropathy].
2001 Jun
Mode of administration-dependent pharmacokinetics of bisphosphonates and bioavailability determination.
2001 Jun 4
Use of bisphosphonates for the treatment of metastatic bone pain. A survey of palliative physicians in the UK.
2001 Mar
Effect of pamidronate in preventing local bone loss after total hip arthroplasty: a randomized, double-blind, controlled trial.
2001 Mar
Bisphosphonate treatment inhibits the growth of prostate cancer cells.
2001 Mar 15
[Two cases of effective weekly paclitaxel administration for metastatic breast cancer].
2001 Nov
Bisphosphonates in the treatment of Charcot neuroarthropathy: a double-blind randomised controlled trial.
2001 Nov
Targeting of tumor cells for human gammadelta T cells by nonpeptide antigens.
2001 Nov 1
Paget's disease of the spine and its management.
2001 Oct
Nitrogen-containing bisphosphonates induce apoptosis of Caco-2 cells in vitro by inhibiting the mevalonate pathway: a model of bisphosphonate-induced gastrointestinal toxicity.
2001 Oct
Pamidronate-induced remission of pain associated with hypertrophic pulmonary osteoarthropathy in chemoendocrine therapy-refractory inoperable metastatic breast carcinoma.
2001 Oct
The use of a whole body index with bone scintigraphy to monitor the response to therapy in Paget's disease.
2001 Oct
Prevention of bone loss and fracture after lung transplantation: a pilot study.
2001 Oct 15
Hypercalcemia in patients with oral squamous cell carcinoma.
2001 Sep
Intravenous pamidronate reduces osteoporosis and improves formation of the regenerate during distraction osteogenesis. A study in immature rabbits.
2001 Sep
Bisphosphonates and nephrocalcinosis in a rabbit leg lengthening model: a histological and therapeutic comparison.
2001 Sep
Bisphosphonates for osteoporosis.
2001 Sep
Trastuzumab and breast cancer.
2001 Sep 27
Bone loss accompanying medical therapies.
2001 Sep 27
Bisphosphonates are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase.
2001 Sep 7
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.
Name Type Language
PAMIDRONATE MONOSODIUM
Common Name English
J710.127I
Code English
PHOSPHONIC ACID, (3-AMINO-1-HYDROXYPROPYLIDENE)BIS-, MONOSODIUM SALT
Systematic Name English
3-AMINO-1-HYDROXY-1,1-PROPANEDIPHOSPHONIC ACID MONOSODIUM SALT
Systematic Name English
PAMIDRONIC ACID MONOSODIUM SALT
Common Name English
Code System Code Type Description
EVMPD
SUB26399
Created by admin on Sat Dec 16 08:46:13 GMT 2023 , Edited by admin on Sat Dec 16 08:46:13 GMT 2023
PRIMARY
PUBCHEM
14157377
Created by admin on Sat Dec 16 08:46:13 GMT 2023 , Edited by admin on Sat Dec 16 08:46:13 GMT 2023
PRIMARY
FDA UNII
MUA93Q6K1J
Created by admin on Sat Dec 16 08:46:13 GMT 2023 , Edited by admin on Sat Dec 16 08:46:13 GMT 2023
PRIMARY
CAS
89131-02-2
Created by admin on Sat Dec 16 08:46:13 GMT 2023 , Edited by admin on Sat Dec 16 08:46:13 GMT 2023
PRIMARY