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| 25mg |
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Ibandronate sodium (Bonviva Sodium), the sodium salt of ibandronate, is a potent inhibitor of FDPS (farnesyl diphosphate synthase) with an IC50 of 20 nM. It is a bisphosphonate drug used in the prevention and treatment of osteoporosis and metastasis-associated skeletal fractures in people with cancer. Ibandronate may also be used to treat hypercalcemia (elevated blood calcium levels). In May 2003, the U.S. Food and Drug Administration (FDA) approved Ibandronate as a daily treatment for post-menopausal osteoporosis.
Ibandronate sodium is a nitrogen-containing third-generation bisphosphonate drug and the sodium salt form of ibandronic acid. This drug inhibits osteoclast-mediated bone resorption and increases bone mineral density. It is indicated for the treatment of postmenopausal osteoporosis, prevention of skeletal-related events in breast cancer patients with bone metastases, and treatment of malignancy-associated hypercalcemia. Ibandronate sodium has high water solubility and can be administered orally or intravenously. This compound is marketed globally under brand names such as Boniva® and Bonviva®.| Targets |
The primary molecular target of ibandronate sodium is farnesyl pyrophosphate synthase (FPPS), a key branch-point enzyme in the mevalonate pathway. By inhibiting FPPS, ibandronate sodium prevents the biosynthesis of isoprenoid lipids (FPP and GGPP), which are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signaling proteins in osteoclasts. Additionally, ibandronate sodium exhibits high affinity for hydroxyapatite crystals in the bone matrix and selectively adsorbs to bone surfaces, enabling targeted distribution to bone tissue. Recent studies have also revealed that ibandronate sodium may exert anti-inflammatory effects by inhibiting the TLRs/MyD88/NF-κB signaling pathway.
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| ln Vitro |
In vitro studies demonstrate that ibandronate sodium exhibits multiple biological activities. At 1.25-2 μM, ibandronate significantly slows endothelial cell growth; at 2 μM, it also reduces capillary-like tube formation and accelerates endothelial cell apoptosis. Ibandronate (<100 μM) dose-dependently increases VEGF expression in endothelial cells and inhibits the proliferation of LNCaP and PC-3 prostate cancer cell lines. In MDCK renal cells, ibandronate inhibits large-conductance and intermediate-conductance calcium-activated potassium channels, with a dissociation constant (KD) of 12.2 μM. In in vitro bone cell cultures, ibandronate (10⁻⁵ M) downregulates IL-1β, RANKL, and TNF-α expression, and inhibits cathepsin K expression. Ibandronate also exerts a protective effect on articular chondrocytes.
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| ln Vivo |
In vivo studies demonstrate that ibandronate sodium exhibits significant anti-resorptive effects in various animal models. In estrogen-depleted rats, dogs, and monkeys, as well as in prednisone-induced bone loss minipigs, ibandronate reduces bone turnover, increases bone mineral density, and maintains bone quality in a dose-dependent manner. In rat models of knee osteoarthritis, ibandronate (20-30 g/kg) improves joint function scores, reduces cartilage damage severity, and increases bone mineral density and bone volume fraction. In patients with postmenopausal osteoporosis, intravenous ibandronate 3 mg every three months for 12 months increases lumbar spine BMD by 4.29% and hip BMD by 2.20%. Within one week after treatment, median serum CTX, a bone resorption marker, decreases by 86.9%.
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| Enzyme Assay |
The inhibitory activity of ibandronate sodium against FPPS is typically assessed using the following protocol:
Target Enzyme Preparation: Recombinantly express human or rat farnesyl pyrophosphate synthase in E. coli and purify by affinity chromatography.
Radiolabeled Substrate: Use [¹⁴C]-isopentenyl pyrophosphate or [³H]-geranyl pyrophosphate as the radiolabeled substrate.
Inhibitor Incubation: Pre-incubate varying concentrations of ibandronate sodium (0.1 nM-100 μM) with FPPS enzyme in reaction buffer for 10-30 minutes.
Reaction Initiation and Termination: Initiate the enzymatic reaction by adding substrate, incubate at 37°C for appropriate duration, then terminate by heating or acid addition.
Product Detection: Measure the amount of radioactive product generated by liquid scintillation counting, or quantify products by LC-MS/MS.
Data Analysis: Plot concentration-inhibition curves to calculate IC₅₀ values and inhibition constant Ki values.
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| Cell Assay |
Cell Culture: Culture rat bone marrow-derived osteoclasts or MDCK renal cells in DMEM containing 10% fetal bovine serum at 37°C in a 5% CO₂ incubator.
Drug Treatment: Add varying concentrations of ibandronate sodium (e.g., 10⁻⁵ M, 1.25-100 μM) and incubate for 24-96 hours.
Viability Assay: Measure cell viability using MTT or CCK-8 assays.
Potassium Channel Activity Assay: Record voltage-gated potassium currents and calcium-activated potassium channel activity using whole-cell patch-clamp technique.
Cytokine Detection: Collect cell supernatants and measure IL-1β, TNF-α, and RANKL levels by ELISA.
Apoptosis Detection: Detect apoptosis using Annexin V-FITC/PI double staining or cathepsin K flow cytometry.
Protein Expression Analysis: Detect TLR4, MyD88, NF-κB, and signaling pathway proteins by Western blot.
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| Animal Protocol |
Animal Selection: Use Sprague-Dawley rats, Beagle dogs, minipigs, or rhesus monkeys.
Model Establishment:
Osteoporosis model: Bilateral ovariectomy in female rats to induce bone loss
Osteoarthritis model: Medial meniscus destabilization surgery to induce knee osteoarthritis
Glucocorticoid model: Prednisone administration in minipigs to induce bone loss
Dosing Regimen: Ibandronate sodium can be administered via subcutaneous injection (0.001-1 mg/kg), intravenous injection (3 mg human equivalent), or oral administration, with dosing intervals ranging from daily to once every three months.
Efficacy Assessment:
Dual-energy X-ray absorptiometry for bone mineral density measurement
ELISA for bone turnover markers (sCTX, osteocalcin)
Micro-CT analysis for trabecular bone structure parameters
Histopathology for cartilage damage assessment and Mankin scoring
Data Analysis: Compare BMD, bone turnover markers, and histological parameters between treatment and model/control groups.
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| ADME/Pharmacokinetics |
Ibandronate sodium is rapidly absorbed after oral administration with a Tmax of approximately 1 hour, but oral bioavailability is very low (approximately 0.63%), and food can further reduce it by about 90%. Following intravenous administration, pharmacokinetics are linear and dose-dependent: AUC₀-∞ values for 2 mg and 6 mg groups are 333.4 and 939.1 ng·h/mL, respectively. Ibandronate is not metabolized in the body, with approximately 55% excreted unchanged in the urine. Plasma protein binding is very high (85.7-99.5%), with a large volume of distribution (90-368 L). The terminal half-life is long, ranging from 37-157 hours. Clearance is significantly positively correlated with creatinine clearance, and patients with renal impairment (creatinine clearance <30 mL/min) show an approximately 60% increase in AUC.
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| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation Ibandronate sodium has a low oral absorption rate (average absorption rate of 6% in adults on an empty stomach, and almost no absorption when taken with food), therefore breastfed infants are unlikely to absorb ibandronate sodium. However, since there is currently no information on the use of ibandronate sodium during lactation, other medications may be preferred, especially for breastfed newborns or premature infants. ◉ Effects on Breastfed Infants No published information found as of the revision date. ◉ Effects on Lactation and Breast Milk No published information found as of the revision date. Ibandronate sodium is generally well-tolerated in clinical studies. Common adverse reactions include myalgia, flu-like symptoms (approximately 33.3% incidence), hypocalcemia, limb pain, and back pain. Intravenous administration may cause transient decreases in blood calcium levels. Rare but serious adverse reactions include osteonecrosis of the jaw. Laboratory studies demonstrate that ibandronate (10⁻⁵ M) inhibits IL-1β, TNF-α, and RANKL expression in bone cells, and downregulates cathepsin K, which may limit bone remodeling and healing capacity, contributing to the pathogenesis of osteonecrosis of the jaw. Regarding nephrotoxicity, studies show that ibandronate inhibits calcium-activated potassium channels in MDCK renal cells; however, clinical studies demonstrate no significant changes in renal function, with median eGFR remaining unchanged from baseline to 12 months. Caution should be exercised in patients with renal impairment. |
| References | |
| Additional Infomation |
Ibandronate sodium is the sodium salt form of ibandronate, a synthetic nitrogenous bisphosphonate. Ibandronate inhibits farnesyl pyrophosphate synthase, leading to a reduction in geraniol-geraniol GTPase signaling protein and inducing osteoclast apoptosis. This drug increases bone mineral density, reduces bone remodeling, inhibits osteoclast-mediated bone resorption, and alleviates metastasis-related and corticosteroid-related bone pain. Aminobisphosphonates are potent bone resorption inhibitors. They are used to treat hypercalcemia associated with malignancies, prevent fractures and skeletal complications in patients with breast cancer bone metastases, and treat and prevent postmenopausal osteoporosis. See also: Ibandronate (with active ingredient). Drug Indications Treatment of osteoporosis in postmenopausal women with increased fracture risk (see Section 5.1). It has been shown to reduce the risk of vertebral fractures, but its efficacy in femoral neck fractures has not been established.
Bondronate sodium is indicated for: prevention of skeletal events (pathological fractures, skeletal complications requiring radiation therapy or surgery) in patients with breast cancer bone metastases; and treatment of hypercalcemia caused by tumors with or without metastases. |
| Molecular Formula |
C9H22NNAO7P2
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|---|---|
| Molecular Weight |
341.2108
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| Exact Mass |
341.076
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| Elemental Analysis |
C, 29.76; H, 5.83; N, 3.86; Na, 12.66; O, 30.84; P, 17.06
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| CAS # |
138844-81-2
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| Related CAS # |
Ibandronate Sodium Monohydrate;138926-19-9;Ibandronic acid;114084-78-5;138844-81-2 (sodium); 155453-10-4 (sodium hemihydrate);
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| PubChem CID |
23670359
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| Appearance |
Typically exists as solid at room temperature
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| Boiling Point |
587.8ºC at 760 mmHg
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| Flash Point |
309.3ºC
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| Vapour Pressure |
2.88E-16mmHg at 25°C
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| LogP |
0.938
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
20
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| Complexity |
377
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| Defined Atom Stereocenter Count |
0
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| SMILES |
P(C(C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])(O[H])P(=O)(O[H])O[H])(=O)(O[H])[O-].[Na+]
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| InChi Key |
LXLBEOAZMZAZND-UHFFFAOYSA-M
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| InChi Code |
InChI=1S/C9H23NO7P2.Na/c1-3-4-5-7-10(2)8-6-9(11,18(12,13)14)19(15,16)17;/h11H,3-8H2,1-2H3,(H2,12,13,14)(H2,15,16,17);/q;+1/p-1
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| Chemical Name |
sodium;hydroxy-[1-hydroxy-3-[methyl(pentyl)amino]-1-phosphonopropyl]phosphinate
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| Synonyms |
Ibandronate sodium anhydrous; 23Y0B94E49; RefChem:923249; 138844-81-2; Bondronat
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9307 mL | 14.6537 mL | 29.3075 mL | |
| 5 mM | 0.5861 mL | 2.9307 mL | 5.8615 mL | |
| 10 mM | 0.2931 mL | 1.4654 mL | 2.9307 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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