Absorption, Distribution and Excretion
The Cmax and AUC of calcium edetate sodium depend on renal function. 5% of the oral dose is absorbed via the gastrointestinal tract. 95% of calcium edetate sodium is excreted in the urine within 24 hours. In rats, 88.32% is recovered in feces and 10.30% in urine after oral administration. The volume of distribution of calcium edetate sodium is 0.19 ± 0.10 L/kg. The mean clearance of edetate sodium in 1-month-old rats is 54.6 mL/min/1.73 m². The mean clearance in adults aged 2–17 years is 113.9 ± 24.4 mL/min/1.73 m². Absorption of calcium edetate sodium in the gastrointestinal tract is poor. Absorption is good after intramuscular or subcutaneous injection. When calcium edetate sodium is administered intravenously to treat lead poisoning, urinary excretion of chelated lead begins within approximately 1 hour and reaches peak excretion within 24–48 hours. Abdominal pain caused by lead poisoning may disappear within 2 hours, muscle weakness and tremors disappear after 4–5 days, and fecal porphyria and stippled red blood cells typically decrease within 4–9 days after the start of treatment. Calcium edetate sodium is primarily distributed in the extracellular fluid. The drug does not penetrate red blood cells…
After parenteral administration, the drug is rapidly filtered by the glomeruli and excreted in the urine either unchanged or as a metal chelate. After intravenous administration, 50% of the dose appears in the urine within 1 hour, and 95% within 24 hours. Changes in urine flow rate and/or pH do not affect the excretion rate of calcium edetate sodium, but impaired renal function with a decreased glomerular filtration rate may delay drug excretion, potentially increasing its nephrotoxicity. For more complete data on the absorption, distribution, and excretion of calcium edetate (10 items in total), please visit the HSDB record page.

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Metabolism/Metabolites
Calcium edetate is almost entirely not metabolized in the body.
Calcium edetate is not metabolized.

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Biological Half-Life
The half-life of calcium edetate is 20–60 minutes.
It has been reported that the plasma half-life of this drug is 20–60 minutes after intravenous injection and 1.5 hours after intramuscular injection.

Interactions
Zinc supplementation (concomitant use may reduce the efficacy of calcium edetate and zinc supplementation due to chelation; zinc supplementation should be discontinued after calcium edetate treatment is completed.)
Calcium edetate interferes with the action of zinc insulin preparations by chelating zinc.
Compared to calcium edetate alone, concomitant use of calcium edetate and dimercaprol (BAL) increases the rate of lead mobilization from tissue deposits and may reduce the incidence of central nervous system toxicity.
Steroids can enhance the nephrotoxicity of calcium edetate in animals.

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Non-human toxicity values
Oral LD50 in rats: 10 g/kg
Intraperitoneal LD50 in rats: 3.85 g/kg
Intravenous LD50 in rats: 3 g/kg
LD50 in mice (ip): 4.5 g/kg
For more complete non-human toxicity data for disodium calcium EDTA (6 in total), please visit the HSDB record page.

Calcium disodium ethylenediaminetetraacetate (EDTA) is the organic calcium salt of disodium ethylenediaminetetraacetate (EDTA). It is a chelating agent used to treat lead poisoning. It has anti-aging, chelating, and detoxifying effects. It contains anhydrous EDTA. Calcium disodium ethylenediaminetetraacetate is a metal ion chelating agent used to reduce the concentration of lead in the blood and remove lead stores from the body. It is listed in the World Health Organization's Essential Medicines List. Calcium disodium ethylenediaminetetraacetate was approved by the U.S. Food and Drug Administration (FDA) on July 16, 1953. Calcium disodium ethylenediaminetetraacetate is the abbreviation for ethylenediaminetetraacetate, a substance used as a chelating agent for lead and some other heavy metals. Its chemical formula is C10H12CaN2Na2O8. It is a chelating agent that can chelate various polyvalent cations, such as calcium. It is used in pharmaceutical production and food additives. Drug Indications Calcium edetate sodium is used to reduce blood lead levels and lead stores in patients with acute and chronic lead poisoning. Mechanism of Action Calcium edetate sodium is distributed in tissues such as the kidneys and bones, chelating lead ions. These lead ions are then excreted in the normal urine with calcium edetate. Lead in some tissues (such as the liver and bones) may redistribute to other tissues after treatment with calcium edetate sodium, but lead levels do not decrease to those of patients who have not been exposed to lead. The calcium in calcium edetate sodium can be replaced by divalent and trivalent metals (especially lead), forming stable soluble complexes that are then excreted in the urine. Unlike disodium edetate (which is no longer sold in the US), calcium disodium edetate is calcium-saturated, allowing for relatively large intravenous injections without significant changes in serum or systemic calcium concentrations. Although theoretically 1 gram of calcium disodium edetate can chelate 620 mg of lead, in patients with acute lead poisoning symptoms or high lead concentrations in soft tissues, only an average of 3-5 mg of lead is excreted in the urine after parenteral administration of 1 gram of this drug. Parenteral administration of calcium disodium edetate can chelate zinc and significantly increase urinary zinc excretion, with a smaller effect on the excretion of cadmium, manganese, iron, and copper. The chelating effect of calcium disodium edetate can increase the excretion of uranium, plutonium, yttrium, and some other heavier radioactive isotopes to some extent. Although in vitro experiments show that mercury readily displaces calcium from calcium disodium edetate, patients with mercury poisoning do not respond to this drug. The pharmacological action of calcium disodium edetate is due to its chelation with divalent and trivalent metals. Any metal capable of displacing calcium from the molecule can form a stable chelate with calcium disodium edetate; lead, zinc, cadmium, manganese, iron, and mercury all possess this property. The mobilization of manganese and iron is not significant. Copper is not mobilized, while mercury cannot be chelated because it binds too tightly to ligands in the body or is stored in inaccessible body cavities. Intravenous administration of calcium edetate does not increase calcium excretion, but zinc excretion increases significantly. The primary source of lead chelated by calcium edetate is bone; subsequently, when chelation therapy ceases, lead in soft tissues redistributes to the bones. Kidney lead levels also decrease after chelation therapy. For more complete data on the mechanisms of action of calcium disodium EDTA (6 types), please visit the HSDB records page.

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Therapeutic Use
Calcium disodium EDTA is indicated for reducing blood lead levels and lead stores in children and adults with lead poisoning (acute and chronic) and lead encephalopathy. Chelation therapy should not replace effective measures to eliminate or reduce further lead exposure. /US Product Label Contains/
The US Food and Drug Administration (FDA) states that the safety and efficacy of calcium edetate sodium for removing heavy metals (such as mercury) and toxins from the body, treating coronary artery disease, or for other uses not described on the manufacturer's label have not been established.
Veterinary: Lead poisoning chelator.
/SRP: Previous Use/ The EDTA lead mobilization test has been shown to be a sensitive indicator of excessive lead storage in the body. This test was used to evaluate the previous cumulative lead absorption in 48 male patients diagnosed with essential hypertension (a condition considered a complication of lead poisoning).
For more complete data on therapeutic uses of calcium disodium EDTA (out of 8), please visit the HSDB record page.

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Drug Warning
/Black Box Warning/ Warning: Calcium disodium EDTA may have toxic effects and can be fatal. Lead encephalopathy is relatively rare in adults but more common in children, and it may be in its early stages and therefore easily overlooked. Mortality rates in children have consistently been high. Patients with lead encephalopathy and cerebral edema may experience fatal increases in intracranial pressure after intravenous infusion; intramuscular injection is the preferred route of administration for these patients. If intravenous infusion is necessary, avoid rapid infusion. Strictly adhere to the dosage regimen and never exceed the recommended daily dose. Fatal medication errors have occurred due to confusion between calcium edetate (EDTA calcium) and disodium edetate (currently discontinued in the US). Children and adults have been mistakenly given disodium edetate instead of calcium edetate; at least five deaths were due to misuse of disodium edetate. Although both calcium edetate and disodium edetate are heavy metal antagonists, they were initially approved by the US Food and Drug Administration (FDA) for different purposes and have different effects; disodium edetate was previously approved by the FDA for the emergency treatment of hypercalcemia in certain patients or for controlling ventricular arrhythmias associated with cardiac glycoside poisoning. Use of disodium edetate can cause a significant, sometimes fatal, decrease in serum calcium levels. In June 2008, after reviewing the risk-benefit ratio of disodium edetate, the FDA revoked its previous approval of the drug due to safety concerns. The FDA stated that it was not considering further action on calcium disodium edetate at that time; most deaths due to the use of EDTA drugs were related to medication errors, specifically the misuse of disodium edetate instead of calcium disodium edetate. The FDA had not received any reports of medication errors resulting in death due to the use of calcium disodium edetate. The manufacturer states that this drug is contraindicated in patients with anuria and active kidney disease. Calcium disodium edetate is contraindicated in patients with hepatitis. The main and most serious toxic effect of calcium disodium edetate is renal tubular necrosis, which often occurs with excessive daily doses and can lead to fatal kidney disease. Calcium disodium edetate may produce the same kidney damage symptoms as lead poisoning, such as proteinuria and microscopic hematuria. In rare cases, distal tubular and glomerular changes, glycosuria, abundant renal epithelial cells in the urine sediment, urinary frequency, and urgency may occur. Proximal renal tubular cell edema and degeneration may also occur; however, this usually resolves upon discontinuation of the drug. For more complete data on drug warnings for calcium disodium EDTA (24 in total), please visit the HSDB record page.

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Pharmacodynamics
Calcium disodium EDTA is a polyvalent ion chelator used to remove lead from the body after lead poisoning. It has a broad therapeutic index because symptoms are only observed at doses far exceeding the therapeutic level. Its duration of action is long due to the at least one-day dosing interval. Patients should be informed of the risk of increased intracranial pressure associated with intravenous infusion.

C10H14CAN2NA2O9

392.2837

374.001

23411-34-9

6093170

Powder
White powder or flakes

614.2ºC at 760 mmHg

>300

325.2ºC

1.15E-16mmHg at 25°C

0

10

7

23

293

0

[Ca+2].[Na+].[Na+].[O-]C(C([H])([H])N(C([H])([H])C(=O)[O-])C([H])([H])C([H])([H])N(C([H])([H])C(=O)[O-])C([H])([H])C(=O)[O-])=O.O([H])[H]

SHWNNYZBHZIQQV-UHFFFAOYSA-J

InChI=1S/C10H16N2O8.Ca.2Na/c13-7(14)3-11(4-8(15)16)1-2-12(5-9(17)18)6-10(19)20;;;/h1-6H2,(H,13,14)(H,15,16)(H,17,18)(H,19,20);;;/q;+2;2*+1/p-4

calcium;disodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

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.

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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).

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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)

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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).

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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

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)