; HEDPA-d3 (disodium); HEDP-d3 (disodium)) Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C2H3D3NA2O7P2 |
| Molecular Weight | 253.01 |
| Exact Mass | 208.993 |
| CAS # | 358730-93-5 |
| Related CAS # | Etidronic acid disodium;7414-83-7 |
| PubChem CID | 3305 |
| Appearance | White to off-white solid powder |
| Density | 2.1±0.1 g/cm3 |
| Boiling Point | 578.8±60.0 °C at 760 mmHg |
| Melting Point | 198-199 |
| Flash Point | 303.8±32.9 °C |
| Vapour Pressure | 0.0±3.6 mmHg at 25°C |
| Index of Refraction | 1.586 |
| LogP | -3.54 |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 11 |
| Complexity | 211 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | [2H]C([2H])([2H])C(O)(P(=O)(O)O)P(=O)(O)O |
| InChi Key | DBVJJBKOTRCVKF-FIBGUPNXSA-N |
| InChi Code | InChI=1S/C2H8O7P2/c1-2(3,10(4,5)6)11(7,8)9/h3H,1H3,(H2,4,5,6)(H2,7,8,9)/i1D3 |
| Chemical Name | (2,2,2-trideuterio-1-hydroxy-1-phosphonoethyl)phosphonic acid |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1]. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Etidronic acid has an oral bioavailability of 1-10%. Further data regarding pharmacokinetics of etidronic acid are not readily available. Absorbed etidronic acid is eliminated in the urine, while the unabsorbed drug is eliminated in the feces. Etidronic acid has a volume of distribution of 0.3-1.3L/kg. Etidronic acid has a renal clearance of 0.09L/kg/h. THE DISTRIBUTION OF TECHNETIUM-99M HEDP IN NORMAL HUMAN ORGANS WAS MEASURED. THE BONE-SEEKING AGENT (99M)TC-SN-1-HYDROXYETHYLIDENE-1,1-DIPHOSPHONIC ACID UNEXPECTEDLY BINDS TO PARTICLES OF HUMAN ARTICULAR CARTILAGE AS WELL AS CORTICAL BONE IN VITRO. MECHANISMS ADDITIONAL TO THE SIMPLE IONIC ATTRACTION BETWEEN THE PHOSPHONATE GROUPS OF HEDP & METAL CATIONS SUCH AS CA2+ ARE RESPONSIBLE FOR THE UPTAKE OF (99M)TC-HEDP BY BODY TISSUES. THE AFFINITY CONSTANT WHICH CHARACTERIZES THE BINDING OF (99)TC-HYDROXYETHYLENE DIPHOSPHONATE (TC-HEDP) WITH HUMAN SERUM ALBUMIN WAS 7.8X10+4. A SINGLE SLOPE WAS OBTAINED. Metabolism / Metabolites Etidronic acid is not metabolized _in vivo_ Not metabolized. Route of Elimination: Etidronate disodium is not metabolized. Within 24 hours, approximately half the absorbed dose is excreted in urine; the remainder is distributed to bone compartments from which it is slowly eliminated. Unabsorbed drug is excreted intact in the feces. Half Life: In normal subjects, plasma half-life of etidronic acid, based on non-compartmental pharmacokinetics is 1 to 6 hours. Biological Half-Life The half life of etidronate is approximately 1-6 hours. |
| Toxicity/Toxicokinetics |
Toxicity Summary Bisphosphonates, when attached to bone tissue, are absorbed by osteoclasts, the bone cells that breaks down bone tissue. Although the mechanism of action of non-nitrogenous bisphosphonates has not been fully elucidated, available data suggest that they bind strongly to hydroxyapatite crystals in the bone matrix, preferentially at the sites of increased bone turnover and inhibit the formation and dissolution of the crystals. Other actions may include direct inhibition of mature osteoclast function, promotion of osteoclast apoptosis, and interference with osteoblast-mediated osteoclast activation. Etidronic acid does not interfere with bone mineralization. In malignancy-related hypercalcemia, etidronic acid decreases serum calcium by inhibiting tumour-induced bone resorption and reducing calcium flow from the resorbing bone into the blood. Etidronic acid also reduces morbidity of osteolytic bone metastases by inhibiting tumour-induced bone resorption. Etidronic acid may promote osteoclast apoptosis by competing with adenosine triphosphate (ATP) in the cellular energy metabolism. The osteoclast initiates apoptosis and dies, leading to an overall decrease in the breakdown of bone. Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Because no information is available on the use of etidronate during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. However, absorption of etidronate by a breastfed infant is unlikely. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. |
| References |
[1]. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216. |
| Additional Infomation |
Therapeutic Uses Chelating Agents EXPTL USE: 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID, DICHLOROMETHANEDIPHOSPHONIC ACID OR THEIR SALTS OR ESTERS REDUCED THE INCIDENCE OF TUMOR CELL METASTASIS IN BONE IN HUMANS. BONE SCANNING AGENT WHEN LABELED WITH (99M)TECHNETIUM CHELATING AGENT; CALCIUM REGULATING AGENT IN HUMAN MEDICINE MEDICATION (VET): 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID, DICHLOROMETHANEDIPHOSPHONIC ACID OR THEIR SALTS OR ESTERS REDUCED THE INCIDENCE OF TUMOR CELL METASTASIS IN BONE IN ANIMALS. Pharmacodynamics Etidronic acid is a first generation bisphosphonate that inhibits the action of osteoclasts, preventing bone resporption. It has a wide therapeutic index as overdoses are not associated with severe toxicity and a long duration of action as it slowly releases from the bone. Patients should be counselled regarding the risk of upper gastrointestinal adverse reactions. |
Solubility Data
| 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 |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9524 mL | 19.7621 mL | 39.5241 mL | |
| 5 mM | 0.7905 mL | 3.9524 mL | 7.9048 mL | |
| 10 mM | 0.3952 mL | 1.9762 mL | 3.9524 mL |