| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
The bioavailability of clodronate via oral administration is 1-2%. A 200 mg intravenous dose achieves a Cmax of 16.1 mg/L and an AUC of 44.2 mgh/L. A 200 mg intramuscular dose achieves a Cmax of 12.8 mg/L and an AUC of 47.5 mgh/L. Further pharmacokinetic data for clodronate are currently unavailable. Clodronate is excreted unchanged in the urine. The renal clearance of clodronate is approximately 90 mL/min. Metabolism/Metabolites Clodronate is not metabolized in the human body. It is metabolized intracellularly to the β-γ-methylene (AppCp type) analog of ATP (AppCCl2p), which is cytotoxic to macrophages in vitro. Half-life: Approximately 13 hours. Biological Half-life The mean plasma half-life of clodronate is 5.6 hours. |
|---|---|
| Toxicity/Toxicokinetics |
Toxicity Summary
Bisphosphonate groups bind strongly to the bone mineral hydroxyapatite. This explains the specific pharmacological effects of these compounds on mineralized tissues, particularly bone. The exact mechanism of action of clophosphonates is unclear, but it is known that it does not inhibit protein isoprenylation, but is instead metabolized intracellularly to the β-γ-methylene (AppCp-type) analogue of ATP (AppCCl2p), which is cytotoxic to macrophages in vitro. The inhibition of ADP/ATP translocases by the metabolite AppCCl2p may be one pathway by which clophosphonates induce osteoclast apoptosis and inhibit bone resorption. Recent studies have shown that the slime mold Discoidus spp. can take up bisphosphonates via pinocytosis. In these cells, clophosphonates (rather than other pharmacologically active bisphosphonates) are incorporated into adenine nucleotides, which may explain why this bisphosphonate sometimes exhibits different effects than other bisphosphonates. Like all bisphosphonates, clophosphonates also bind to protein tyrosine phosphatases. Protein binding Clodronic acid has a protein binding rate of 36% in plasma. |
| References | |
| Additional Infomation |
Pharmacodynamics
Clodronate is a first-generation bisphosphonate that inhibits osteoclast-mediated bone resorption. Because large overdose doses are required to cause significant toxicity, and the drug is slowly released from bone, it has a wide therapeutic index and a long duration of action. Patients should be informed of the risks of hypocalcemia, hypovolemia, renal insufficiency, transient hyperphosphatemia, and transient hyperparathyroidism. |
| Molecular Formula |
CH4O6P2CL2
|
|---|---|
| Molecular Weight |
244.89246
|
| Exact Mass |
243.886
|
| CAS # |
10596-23-3
|
| Related CAS # |
Clodronate disodium tetrahydrate;88416-50-6;Clodronic acid disodium salt;22560-50-5
|
| PubChem CID |
25419
|
| Appearance |
Colorless to light yellow liquid（Density：2.306±0.06 g/cm3）
|
| Density |
2.3±0.1 g/cm3
|
| Boiling Point |
474.7±55.0 °C at 760 mmHg
|
| Melting Point |
249-251°
|
| Flash Point |
240.9±31.5 °C
|
| Vapour Pressure |
0.0±2.5 mmHg at 25°C
|
| Index of Refraction |
1.598
|
| LogP |
-2.38
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
11
|
| Complexity |
211
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC(P(O)(O)=O)(P(O)(O)=O)Cl
|
| InChi Key |
ACSIXWWBWUQEHA-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/CH4Cl2O6P2/c2-1(3,10(4,5)6)11(7,8)9/h(H2,4,5,6)(H2,7,8,9)
|
| Chemical Name |
[dichloro(phosphono)methyl]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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 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
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 | 4.0835 mL | 20.4173 mL | 40.8347 mL | |
| 5 mM | 0.8167 mL | 4.0835 mL | 8.1669 mL | |
| 10 mM | 0.4083 mL | 2.0417 mL | 4.0835 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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