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
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
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
55.9 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | PAMIDRONATE DISODIUM Approved UseHypercalcemia 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 Date1991 |
|||
Primary | PAMIDRONATE DISODIUM Approved UseHypercalcemia 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 Date1991 |
|||
Primary | PAMIDRONATE DISODIUM Approved UseHypercalcemia 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 Date1991 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.92 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9115053/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
10.2 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9115053/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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 Sources: Hypotension Taste perversion |
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 Sources: Hypocalcemia Bone pain |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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: |
PubMed
Title | Date | PubMed |
---|---|---|
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
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21856057
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
Edited
Fri Dec 15 16:09:01 GMT 2023
by
admin
on
Fri Dec 15 16:09:01 GMT 2023
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Record UNII |
C7S8VWP5DH
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C443
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NCI_THESAURUS |
C67439
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260-647-1
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722600
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100000092120
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4673
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C7S8VWP5DH
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57248-88-1
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SUB21795
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m8374
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PRIMARY | Merck Index |
Related Record | Type | Details | ||
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PARENT -> SALT/SOLVATE | |||
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SOLVATE->ANHYDROUS |
Related Record | Type | Details | ||
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ACTIVE MOIETY |