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
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
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 |
---|---|---|
[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
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.
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SUB26399
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14157377
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MUA93Q6K1J
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89131-02-2
Created by
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ACTIVE MOIETY
SUBSTANCE RECORD