Details
Stereochemistry | ACHIRAL |
Molecular Formula | C5H10N2O7P2 |
Molecular Weight | 272.0896 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(CN1C=CN=C1)(P(O)(O)=O)P(O)(O)=O
InChI
InChIKey=XRASPMIURGNCCH-UHFFFAOYSA-N
InChI=1S/C5H10N2O7P2/c8-5(15(9,10)11,16(12,13)14)3-7-2-1-6-4-7/h1-2,4,8H,3H2,(H2,9,10,11)(H2,12,13,14)
Molecular Formula | C5H10N2O7P2 |
Molecular Weight | 272.0896 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Zoledronic acid (Reclast, Aclasta, Zometa) is an intravenous, highly potent amino-bisphosphonate approved worldwide, including in the USA, EU and Japan for use in patients with primary or secondary osteoporosis or low bone mass (approved indications vary between countries). Its high affinity to and long half-life in bone, and long duration of action allow for once-yearly administration, which has the potential to improve adherence to therapy. Zoledronic acid once yearly for up to 3 years improved bone mineral density (BMD) at several skeletal sites, reduced fracture risk and bone turnover, and/or preserved
bone structure and mass relative to placebo in clinical studies in patients with primary or secondary osteoporosis. While additional benefits were seen when treatment was continued for up to 6 years, as evidenced by a reduced risk of vertebral fractures and higher BMD relative to 3 years’ therapy, there was the minimal advantage of treatment beyond 6 years. Therefore, in patients with low fracture risk, treatment discontinuation should be considered after approximately 5 years’ therapy. Zoledronic acid administered annually or once in 2 years was also effective in preventing bone loss in patients with low bone mass. Zoledronic acid was generally well tolerated, with the most common adverse events (AEs) being transient, mild-to-moderate post-infusion symptoms, which decreased with subsequent infusions.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1782 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22390415 |
4.1 nM [IC50] | ||
Target ID: CHEMBL4769 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17535895 |
97.0 µM [IC50] | ||
Target ID: CHEMBL3510 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24813742 |
92.0 nM [IC50] | ||
Target ID: CHEMBL205 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24650641 |
62.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Zometa Approved UseINDICATIONS AND USAGE
Hypercalcemia of Malignancy. Zometa® (zoledronic acid for injection) is indicated for the treatment of hypercalcemia of malignancy. 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 dequately 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 Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established.
Multiple Myeloma and Bone Metastases of Solid Tumors. Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy Launch Date2001 |
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Primary | Zometa Approved UseINDICATIONS AND USAGE
Hypercalcemia of Malignancy. Zometa® (zoledronic acid for injection) is indicated for the treatment of hypercalcemia of malignancy. 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 dequately 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 Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established.
Multiple Myeloma and Bone Metastases of Solid Tumors. Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy Launch Date2001 |
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Primary | Zometa Approved UseINDICATIONS AND USAGE
Hypercalcemia of Malignancy. Zometa® (zoledronic acid for injection) is indicated for the treatment of hypercalcemia of malignancy. 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 dequately 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 Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established.
Multiple Myeloma and Bone Metastases of Solid Tumors. Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy Launch Date2001 |
|||
Primary | Zometa Approved UseINDICATIONS AND USAGE
Hypercalcemia of Malignancy. Zometa® (zoledronic acid for injection) is indicated for the treatment of hypercalcemia of malignancy. 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 dequately 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 Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established.
Multiple Myeloma and Bone Metastases of Solid Tumors. Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy Launch Date2001 |
|||
Primary | Zometa Approved UseINDICATIONS AND USAGE
Hypercalcemia of Malignancy. Zometa® (zoledronic acid for injection) is indicated for the treatment of hypercalcemia of malignancy. 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 dequately 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 Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established.
Multiple Myeloma and Bone Metastases of Solid Tumors. Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy Launch Date2001 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
264 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21563999 |
4 mg single, intravenous dose: 4 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
ZOLEDRONIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
420 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21563999 |
4 mg single, intravenous dose: 4 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
ZOLEDRONIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
39 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21563999 |
4 mg single, intravenous dose: 4 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
ZOLEDRONIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
16 mg 1 times / 4 weeks multiple, intravenous Highest studied dose Dose: 16 mg, 1 times / 4 weeks Route: intravenous Route: multiple Dose: 16 mg, 1 times / 4 weeks Sources: |
unhealthy, 40-79 years Health Status: unhealthy Age Group: 40-79 years Sex: M+F Sources: |
|
16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) Health Status: unhealthy Age Group: 54 years (range: 34–73 years) Sex: M+F Sources: |
Other AEs: Skeletal pain, Fever... Other AEs: Skeletal pain (30%) Sources: Fever (20%) Anorexia (20%) Diarrhea (20%) Constipation (10%) Nausea (20%) Myalgia (20%) Arthralgia (10%) Anemia (30%) Rigors (20%) Coughing (20%) Leg edema (10%) Urinary tract infection (10%) Fatigue (40%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Arthralgia | 10% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) Health Status: unhealthy Age Group: 54 years (range: 34–73 years) Sex: M+F Sources: |
Constipation | 10% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) Health Status: unhealthy Age Group: 54 years (range: 34–73 years) Sex: M+F Sources: |
Leg edema | 10% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) Health Status: unhealthy Age Group: 54 years (range: 34–73 years) Sex: M+F Sources: |
Urinary tract infection | 10% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) Health Status: unhealthy Age Group: 54 years (range: 34–73 years) Sex: M+F Sources: |
Anorexia | 20% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) Health Status: unhealthy Age Group: 54 years (range: 34–73 years) Sex: M+F Sources: |
Coughing | 20% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) Health Status: unhealthy Age Group: 54 years (range: 34–73 years) Sex: M+F Sources: |
Diarrhea | 20% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) Health Status: unhealthy Age Group: 54 years (range: 34–73 years) Sex: M+F Sources: |
Fever | 20% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) Health Status: unhealthy Age Group: 54 years (range: 34–73 years) Sex: M+F Sources: |
Myalgia | 20% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) Health Status: unhealthy Age Group: 54 years (range: 34–73 years) Sex: M+F Sources: |
Nausea | 20% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) Health Status: unhealthy Age Group: 54 years (range: 34–73 years) Sex: M+F Sources: |
Rigors | 20% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) Health Status: unhealthy Age Group: 54 years (range: 34–73 years) Sex: M+F Sources: |
Anemia | 30% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) Health Status: unhealthy Age Group: 54 years (range: 34–73 years) Sex: M+F Sources: |
Skeletal pain | 30% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) Health Status: unhealthy Age Group: 54 years (range: 34–73 years) Sex: M+F Sources: |
Fatigue | 40% | 16 mg single, intravenous Highest studied dose Dose: 16 mg Route: intravenous Route: single Dose: 16 mg Sources: |
unhealthy, 54 years (range: 34–73 years) Health Status: unhealthy Age Group: 54 years (range: 34–73 years) Sex: M+F Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021817s000_PharmR_P1.pdf#page=50 Page: 50.0 |
no |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no |
PubMed
Title | Date | PubMed |
---|---|---|
Preclinical studies with zoledronic acid and other bisphosphonates: impact on the bone microenvironment. | 2001 Apr |
|
Zoledronic acid in the treatment of hypercalcemia of malignancy: results of the international clinical development program. | 2001 Apr |
|
The role of zoledronic acid in cancer: clinical studies in the treatment and prevention of bone metastases. | 2001 Apr |
|
Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases. | 2001 Apr 1 |
|
Adjuvant bisphosphonate therapy: the future. | 2001 Aug |
|
Analysis of skeletal-related events in breast cancer and response to therapy. | 2001 Aug |
|
Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. | 2001 Feb |
|
A Phase I, open label, dose ranging trial of intravenous bolus zoledronic acid, a novel bisphosphonate, in cancer patients with metastatic bone disease. | 2001 Jan 1 |
|
Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. | 2001 Jan 15 |
|
Safety and efficacy of bisphosphonates beyond 24 months in cancer patients. | 2001 Jul 15 |
|
The effects of MMP inhibitors on human salivary MMP activity and caries progression in rats. | 2001 Jun |
|
FDA grants priority review for ZOMETA. | 2001 Oct |
|
A microcosting analysis of zoledronic acid and pamidronate therapy in patients with metastatic bone disease. | 2001 Oct |
|
From the Food and Drug Administration. | 2001 Oct 3 |
|
Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. | 2001 Sep-Oct |
|
The use of zoledronic acid, a novel, highly potent bisphosphonate, for the treatment of hypercalcemia of malignancy. | 2002 |
|
U.S. Food and Drug Administration drug approval summaries: imatinib mesylate, mesna tablets, and zoledronic acid. | 2002 |
|
Direct effects of bisphosphonates on breast cancer cells. | 2002 |
|
FDA approves ZOMETA for treatment of cancer-related bone complications. | 2002 Apr |
|
Is there a dose response relationship for clodronate in the treatment of tumour induced hypercalcaemia? | 2002 Apr 22 |
|
Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa). | 2002 Aug 15 |
|
Advances in the biology and treatment of myeloma bone disease. | 2002 Dec |
|
The anti-tumour activity of bisphosphonates. | 2002 Dec |
|
The role of osteoclastic activity in prostate cancer skeletal metastases. | 2002 Feb |
|
Distinct mechanisms of bisphosphonate action between osteoblasts and breast cancer cells: identity of a potent new bisphosphonate analogue. | 2002 Feb |
|
Myeloma interacts with the bone marrow microenvironment to induce osteoclastogenesis and is dependent on osteoclast activity. | 2002 Feb |
|
Multiple myeloma: present and future. | 2002 Jan |
|
Osteoporosis: challenges and new opportunities for therapy. | 2002 Jul |
|
Bisphosphonates for cancer patients: why, how, and when? | 2002 Jul |
|
Novel therapeutic options for osteoporosis. | 2002 Jul |
|
Adaptive dose finding for phase I clinical trials of drugs used for chemotherapy of cancer. | 2002 Jul 15 |
|
An investigation of bone resorption and Dictyostelium discoideum growth inhibition by bisphosphonate drugs. | 2002 Jul 4 |
|
Zoledronic acid. A bisphosphonate for hypercalcemia of malignancy and osteolytic metastases. | 2002 Jul-Aug |
|
Novel approaches to the management of bone metastases in patients with breast cancer. | 2002 Jun |
|
Bisphosphonates influence the proliferation and the maturation of normal human osteoblasts. | 2002 Jun |
|
Bisphosphonates pamidronate and zoledronic acid stimulate osteoprotegerin production by primary human osteoblasts. | 2002 Mar 1 |
|
Severe increase in creatinine with hypocalcaemia in thalidomide-treated myeloma patients receiving zoledronic acid infusions. | 2002 Nov |
|
Pamidronate causes apoptosis of plasma cells in vivo in patients with multiple myeloma. | 2002 Nov |
|
Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. | 2002 Nov 15 |
|
The use of bisphosphonates in patients with breast cancer. | 2002 Nov-Dec |
|
Zoledronic acid. | 2002 Nov-Dec |
|
Gateways to clinical trials. | 2002 Oct |
|
Zoledronic acid: new preparation. Just a me-too: no advance in hypercalcemia of malignancy. | 2002 Oct |
|
[Bisphosphonates in bone metastases. Fewer fractures, less pain]. | 2002 Sep 26 |
Patents
Sample Use Guides
The maximum recommended dose of Zometa in hypercalcemia of malignancy is 4 mg. The 4 mg dose must be given as a single-dose intravenous infusion over no less than 15 minutes.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26126921
For the transfection of the T24 human bladder cancer cells, pCMV6 empty vector (OriGene, Rockville, MD, USA) and pCMV6 TAp73 vector were transfected into cells using Lipofectamine™ 2000 (Invitrogen Life Technologies). After 6 h, the medium was refreshed and cultured for 48 h. Then the cells were treated with ZA (200 μM).
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 18:08:29 GMT 2025
by
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Record UNII |
70HZ18PH24
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Record Status |
Validated (UNII)
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Record Version |
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NDF-RT |
N0000175579
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WHO-ATC |
M05BA08
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FDA ORPHAN DRUG |
130899
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NCI_THESAURUS |
C443
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N0000007707
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1546014
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SOLVATE->ANHYDROUS | |||
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SALT/SOLVATE -> PARENT | |||
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BINDER->LIGAND |
Binding to human plasma proteins was low (approximately 22 %) and independent of the concentration of zoledronic acid.
BINDING
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SALT/SOLVATE -> PARENT | |||
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SALT/SOLVATE -> PARENT |
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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