Zoledronic Acid (hydrate)
(Synonyms: 唑来膦酸一水合物; Zoledronate monohydrate; CGP 42446 monohydrate; CGP42446A monohydrate; ZOL 446 monohydrate) 目录号 : GC45187
A bisphosphonate that inhibits bone resorption
Cas No.:165800-06-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Zoledronic acid is a third-generation heterocyclic nitrogen-containing bisphosphonate that inhibits the prenylation of GTPases critical to the signaling events related to osteoclast-mediated bone resorption. It has a high affinity for hydroxyapatite (Ki = 3.47 μM) and binds directly to mineralized bone where it decreases bone resorption by inhibiting osteoclast proliferation and inducing osteoclast apoptosis. At μM concentrations, zoledronic acid demonstrates antitumor effects in vitro against breast, prostate, and myeloma cancer cells by inducing cytostasis and prevents bone metastases through its inhibitory effects on adhesion molecules, tumor cell invasion, and angiogenesis. Zoledronic acid has been used in the treatment of osteoporosis, Paget's disease, metastatic bone disease, multiple myeloma, hypercalcemia of malignancy, and skeletal-related events associated with metastatic castrate-resistant prostate cancer.
| Cas No. | 165800-06-6 | SDF | |
| 别名 | 唑来膦酸一水合物; Zoledronate monohydrate; CGP 42446 monohydrate; CGP42446A monohydrate; ZOL 446 monohydrate | ||
| Canonical SMILES | OP(C(O)(P(O)(O)=O)CN1C=NC=C1)(O)=O.O | ||
| 分子式 | C5H10N2O7P2•H2O | 分子量 | 290.1 |
| 溶解度 | PBS (pH 7.2): 1.6 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.4471 mL | 17.2354 mL | 34.4709 mL |
| 5 mM | 0.6894 mL | 3.4471 mL | 6.8942 mL |
| 10 mM | 0.3447 mL | 1.7235 mL | 3.4471 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Treatment of Hypercalcemia of Malignancy
Endocrinol Metab Clin North Am 2021 Dec;50(4):781-792.PMID:34774248DOI:10.1016/j.ecl.2021.08.002.
The treatment of hypercalcemia of malignancy (HCM) consists of enhancing renal calcium excretion, mostly through hydration with isotonic fluids and the use of antiresorptive therapies. Intravenous Zoledronic Acid is currently the first-line treatment. Subcutaneous denosumab is used for bisphosphonate-refractory hypercalcemia and in patients with renal failure. There is no evidence that bisphosphonates prevent the occurrence of HCM. Conversely, denosumab, compared with Zoledronic Acid, is associated with a lower risk of HCM, both first episode and recurrence, in patients with breast cancer and multiple myeloma.
Hypercalcemia: A Review
JAMA 2022 Oct 25;328(16):1624-1636.PMID:36282253DOI:10.1001/jama.2022.18331.
Importance: Hypercalcemia affects approximately 1% of the worldwide population. Mild hypercalcemia, defined as total calcium of less than 12 mg/dL (<3 mmol/L) or ionized calcium of 5.6 to 8.0 mg/dL (1.4-2 mmol/L), is usually asymptomatic but may be associated with constitutional symptoms such as fatigue and constipation in approximately 20% of people. Hypercalcemia that is severe, defined as total calcium of 14 mg/dL or greater (>3.5 mmol/L) or ionized calcium of 10 mg/dL or greater (≥2.5 mmol/L) or that develops rapidly over days to weeks, can cause nausea, vomiting, dehydration, confusion, somnolence, and coma. Observations: Approximately 90% of people with hypercalcemia have primary hyperparathyroidism (PHPT) or malignancy. Additional causes of hypercalcemia include granulomatous disease such as sarcoidosis, endocrinopathies such as thyroid disease, immobilization, genetic disorders, and medications such as thiazide diuretics and supplements such as calcium, vitamin D, or vitamin A. Hypercalcemia has been associated with sodium-glucose cotransporter 2 protein inhibitors, immune checkpoint inhibitors, denosumab discontinuation, SARS-CoV-2, ketogenic diets, and extreme exercise, but these account for less than 1% of causes. Serum intact parathyroid hormone (PTH), the most important initial test to evaluate hypercalcemia, distinguishes PTH-dependent from PTH-independent causes. In a patient with hypercalcemia, an elevated or normal PTH concentration is consistent with PHPT, while a suppressed PTH level (<20 pg/mL depending on assay) indicates another cause. Mild hypercalcemia usually does not need acute intervention. If due to PHPT, parathyroidectomy may be considered depending on age, serum calcium level, and kidney or skeletal involvement. In patients older than 50 years with serum calcium levels less than 1 mg above the upper normal limit and no evidence of skeletal or kidney disease, observation may be appropriate. Initial therapy of symptomatic or severe hypercalcemia consists of hydration and intravenous bisphosphonates, such as Zoledronic Acid or pamidronate. In patients with kidney failure, denosumab and dialysis may be indicated. Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders, some lymphomas). Treatment reduces serum calcium and improves symptoms, at least transiently. The underlying cause of hypercalcemia should be identified and treated. The prognosis for asymptomatic PHPT is excellent with either medical or surgical management. Hypercalcemia of malignancy is associated with poor survival. Conclusions and relevance: Mild hypercalcemia is typically asymptomatic, while severe hypercalcemia is associated with nausea, vomiting, dehydration, confusion, somnolence, and coma. Asymptomatic hypercalcemia due to primary hyperparathyroidism is managed with parathyroidectomy or observation with monitoring, while severe hypercalcemia is typically treated with hydration and intravenous bisphosphonates.
Zoledronic Acid for prevention and treatment of osteoporosis
Expert Opin Pharmacother 2011 Apr;12(5):807-15.PMID:21385149DOI:10.1517/14656566.2011.562201.
Introduction: Osteoporosis (OP) is associated with a high risk of fracture and disability and with substantial medical costs. This paper is a review of the intravenous (i.v.) bisphosphonate Zoledronic Acid 5 mg (ZOL), used in the treatment and prevention of OP. Areas covered: This is a review of the scientific literature, between 2003 and 2010, on the use of ZOL in patients with low bone mass or OP. Expert opinion: ZOL, given as a single infusion once yearly, has proven efficacy in reducing risk of vertebral and hip fractures in postmenopausal women with OP. In men and women with a recent hip fracture, ZOL has been shown to reduce the incidence of future clinical fractures. Data also demonstrate an increase in bone mineral density in postmenopausal women with osteopenia, in men with OP, and in patients at risk for glucocorticoid-induced osteoporosis. The ZOL clinical program has shown this agent to be safe and generally well tolerated. Acute flu-like symptoms may occur following the first infusion of ZOL, but these are generally mild and transient, and decrease in frequency with subsequent infusions. Patients must have adequate renal function (creatinine clearance ≥ 35 ml/min) and be adequately hydrated prior to infusion. With orally administered bisphosphonates, patient compliance and persistence with weekly or monthly dosing are frequently suboptimal. The ability to administer i.v. ZOL once yearly over 15 min for the treatment of OP provides the advantage of guaranteeing medication compliance for the duration of the dosing interval.
A phase II study of palliative radiotherapy combined with Zoledronic Acid hydrate for metastatic bone tumour from renal cell carcinoma
Jpn J Clin Oncol 2021 Jan 1;51(1):100-105.PMID:32869095DOI:10.1093/jjco/hyaa158.
Purpose: Palliative radiotherapy is the standard of care for bone metastases. However, skeletal-related events, defined as a pathologic fracture, paraplegia, surgery or radiotherapy for local recurrence, or severe pain in previously irradiated bone with radio-resistant histology type still present high incidence. The primary objective of this study was to determine whether Zoledronic Acid hydrate and palliative radiotherapy could prevent local skeletal-related events. Methods: Eligible patients with bone metastases from renal cell carcinoma were treated with Zoledronic Acid hydrate every 3 or 4 weeks and concurrent palliative radiotherapy of 30 Gy in 3 Gy fractions. The criteria for radiotherapy were established by the treating physician, but patients with complicated bone metastases (impending pathological fracture or spinal cord compression) which needed immediate surgery were excluded. The primary endpoint was the local skeletal-related event-free survival rate at 1 year. Results: Twenty-seven patients were included in the study. The median age was 65 (range, 50-84) years. Radiotherapy dose was 30 Gy for all patients except 1 whose radiotherapy was terminated due to brain metastasis progression at 18 Gy. Zoledronic Acid hydrate was administered in a median of 12 (range, 0-34) times. The median follow-up period was 12 months and 19 months in patients who were still alive. Of 27 patients in the efficacy analysis, the 1-year local skeletal-related event-free rate was 77.6% (80% confidence interval, 66.2-89.0). Common grade 3 toxicities were hypocalcemia (1 [4%]), sGPT level increase (1 [4%]) and sGOT level increase (1 [4%]). There was no grade 4 or 5 toxicity. Conclusion: Zoledronic Acid hydrate administration and palliative radiotherapy were a well-tolerated and promising treatment reducing skeletal-related events for bone metastases from renal cell carcinoma.
[Pharmacokinetics of Zoledronic Acid[once-yearly bisphosphonate(intravenous infusion)]]
Clin Calcium 2016;26(11):1605-1613.PMID:27777393doi
Zoledronic Acid hydrate(Zoledronic Acid)is an osteoporosis therapeutic agent which shows the fracture suppression effect with once-yearly intravenous infusion. Although Zoledronic Acid is quickly disappeared from the blood after intravenous infusion, it is taken into the bone immediately and incorporated into the bone tissue. In addition, Zoledronic Acid shows the potent suppression effect on bone resorption by inhibiting farnesyl diphosphate synthase of the mevalonate pathway(FPPS)strongly. In vivo study, the single intravenous administration of Zoledronic Acid to the mature ovariectomized(OVX)rats demonstrated to suppress the decreasing bone strength dose-dependently in 32 weeks, corresponding to more than one year in human. Changes in bone resorption markers in the study of Japanese osteoporosis patients(ZONE Study)indicated that bone resorption inhibition action was maintained also over one year. The fracture suppression and increase of bone density with once-yealy administration was demonstrated in clinical trials in the osteoporosis patients in Japan and other countries, and Zoledronic Acid was currently approved for osteoporosis in September 2016 in Japan. Zoledronic Acid is expected to contribute to the treatment of osteoporosis as a new bisphosphonate with once-yearly administration.