Absorption, Distribution and Excretion
Following intravenous administration, 95% of the dose is excreted in the urine after 24 hours. In rats, after oral administration, the urinary recovery rate was 5.3%, and the fecal recovery rate was 88.5%. The volume of distribution data for anhydrous disodium edetate are not yet clear. The mean clearance of edetate in 1-month-old rats was 54.6 mL/min/1.73 m². The mean clearance in individuals aged 2–17 years was 113.9 ± 24.4 mL/min/1.73 m². Following intravenous administration, the chelates formed are excreted in the urine, with 50% excreted within 1 hour and over 95% within 24 hours. Disodium EDTA…is poorly absorbed in the gastrointestinal tract and has few adverse reactions when used as an excipient in pharmaceutical formulations. Twenty male Sprague-Dawley rats were divided into four groups of five each. Group 1 rats were injected intraperitoneally with disodium 14C EDTA. Group 2 rats had the compound applied to their hairless skin. Group 3 rats had the compound applied to their hairless and abraded skin (abrased every 2 or 3 cm in the treated area). Group 4 was the control group. The specific activity of disodium (14C EDTA) was 21.6 mCi/mM, and it was dissolved in physiological saline to prepare a solution with a concentration of 50 pCi/mL. Animals in the intraperitoneal injection group were injected with 0.5 mL of this solution, i.e., 25 pCi of disodium (14C EDTA). Animals in the topical skin group were given 25 pCi of disodium (14C EDTA) ointment (components: modulan, mineral oil, petrolatum, and cetyl alcohol in a ratio of 35:21:25:12), which was applied to a 50 cm² thin polyethylene film. The film was fixed to the torso of each animal with tape. Rats wore collars around their necks. All animals were euthanized by decapitation 24 hours after administration. 24 hours after intraperitoneal injection of (14)C disodium ethylenediaminetetraacetate, the drug distribution in each tissue (per 100 mg wet weight) was as follows: liver 577±13, small intestine 631±25, large intestine 696±19, kidney 1964±220. 24 hours after application to normal skin, the drug distribution in each tissue was as follows: liver 6±4, small intestine 99±22, large intestine 107±24, kidney 29±12. 24 hours after application to broken skin, the drug distribution in each tissue was as follows: liver 139±34, small intestine 214±76, large intestine 309±115, kidney 222±30.
Researchers reported that rats fed 0.5% (14)C disodium ethylenediaminetetraacetate (EDTA), 1.0%, and 5.0% of the ingested dose for 12 weeks excreted 82.2%, 44.5%, and 45.4% of the ingested dose in urine and feces, respectively. Feces contained 99.4%, 98.2%, and 97.5% of the excrement, respectively, while urine contained 0.6%, 1.8%, and 2.5% of the excrement (corresponding to the respective doses).
For more complete data on the absorption, distribution, and excretion of disodium ethylenediaminetetraacetate (7 types), please visit the HSDB record page.
Metabolism/Metabolites
Ethylenediaminetetraacetate is almost completely not metabolized in vivo.
Biological half-life
After intravenous administration, the chelates formed are excreted in urine, with 50% excreted within 1 hour and over 95% within 24 hours.

Interactions
Researchers reported that disodium EDTA (10 mg/mL) increased the intestinal absorption of neutral, basic, and acidic compounds in male Sprague-Dawley rats. This chelator increased the absorption of (14)C-mannitol and (14)C-inulin from <2% to 7%–1%, (14)CN-methyldecylamine from 2%–3% to 11%–15%, and sulfamethoxam from 11%–14% to 26%–32%. Plasma concentrations of the drugs were increased five to six times compared to the control group.
When 1% (w/v; 24 mM) disodium EDTA was used in combination with 1% (w/v) reduced glutathione, it increased the absorption of acetazolamide in the small intestine of male Charles River rats. Intestinal absorption increased by 1.5 to 2 times; however, treatment with EDTA and glutathione did not affect gastric absorption. Researchers believe that disodium ethylenediaminetetraacetate (EDTA disodium) alters the water permeability of intestinal epithelial cells by chelating magnesium and calcium ions, thereby causing epithelial cell separation.

---

Non-human toxicity values
Mice oral LD50: 400 mg/kg
Rat oral LD50: 3.7 g/kg
Rabbit intravenous LD50: 47 mg/kg
Rabbit oral LD50: 2300 mg/kg
For more complete (8) non-human toxicity values of disodium ethylenediaminetetraacetate (EDTA disodium), please visit the HSDB record page.

[1]. Artifact-inducing enrichment of ethylenediaminetetraacetic acid and ethyleneglycoltetraacetic acid on anion exchange resins. Anal Biochem. 2011 May 1;412(1):34-9.

[2]. The role of ethylenediamine tetraacetic acid (EDTA) as in vitro anticoagulant for diagnostic purposes. Clin Chem Lab Med. 2007;45(5):565-76.

[3]. Chelation therapy in the treatment of cardiovascular diseases. J Clin Lipidol. 2016 Jan-Feb;10(1):58-62.

[4]. The effect of ethylenediaminetetra-acetic acid on the cell walls of some gram-negative bacteria. J Gen Microbiol. 1965 Jun;39(3):385-99.

[5]. Ethylenediaminetetraacetic acid induces antioxidant and anti-inflammatory activities in experimental liver fibrosis. Redox Rep. 2011;16(2):62-70.

[6]. Remediation of heavy metals contaminated silty clay loam soil by column extraction with ethylenediaminetetraacetic acid and nitrilo triacetic acid. Journal of Environmental Engineering, 2017, 143(8): 04017026.

[7]. Ethylenediaminetetraacetic acid (EDTA) enhances cAMP production in human TDAG8-expressing cells. Biochem Biophys Res Commun. 2022 Oct 20;626:15-20.

Anhydrous disodium edetate is a polyvalent chelating agent used to treat hypercalcemia and ventricular arrhythmias associated with digitalis toxicity. Disodium edetate is the disodium salt of edetate, a heavy metal chelating agent with anti-hypercalcemic and antiarrhythmic effects. As a heavy metal antagonist, edetate chelates divalent and trivalent metals to form soluble and stable complexes that are readily excreted by the kidneys, thereby reducing serum calcium concentration. Furthermore, the drug exerts a negative inotropic effect on the heart by transiently inducing a hypocalcemic state, thus antagonizing the positive inotropic and chronotropic effects of digitalis on the ventricles. When edetate is used as eye drops, it exerts its ocular effect by chelating calcium ions to form soluble complexes, thereby clearing corneal calcium deposits. Sodium edetate is a chelating agent that can chelate various polyvalent cations, such as calcium. It is used in pharmaceuticals and food additives. See also: edetate (contains the active ingredient); aloe vera leaf; disodium edetate; glycerin; urea (one of the components).

---

Indications
Disodium edetate is indicated for the emergency treatment of hypercalcemia and ventricular arrhythmias associated with digitalis toxicity.

---

Mechanism of Action
Anhydrous disodium edetate chelates divalent and trivalent ions, such as magnesium, zinc, and calcium. The chelates are excreted in the urine, reducing the concentration of these ions in the blood.
Disodium edetate injection can form chelates with calcium ions and many other divalent and trivalent metal ions. Due to its affinity for calcium ions, intravenous infusion can lower serum calcium levels. Prolonged slow infusion may lead to mobilization of extracirculatory calcium stores. Disodium edetate has a negative inotropic effect on the heart.
Disodium edetate can also form chelates with other polyvalent metal ions and increase the urinary excretion of magnesium, zinc, and other trace elements. It does not form chelates with potassium ions, but it can lower serum potassium levels and increase urinary potassium excretion.

---

Therapeutic Uses
Anticoagulant; Chelating Agent; Food Additive
Endarter (Disodium edetate injection, USP) is indicated for the treatment of emergency hypercalcemia in specific patients and for the control of ventricular arrhythmias associated with digitalis toxicity. /Included in US Product Label/
Disodium edetate can also be used as an anticoagulant because it chelates calcium ions, thereby preventing blood clotting in vitro. A concentration of 0.1% w/v is used for small-dose hematologic tests, and a concentration of 0.3% w/v is used for transfusions.
Disodium edetate is sometimes used to terminate the effects of injected calcium, antagonize digitalis toxicity, or inhibit tachyarrhythmias. /Previous/
For more complete data on the therapeutic uses of disodium EDTA (8 types), please visit the HSDB record page.

---

Drug Warning
/Black Box Warning/ This drug is recommended for specific patients only when the clinical severity is sufficient to support aggressive measures related to this type of treatment.
Clinical studies of disodium EDTA did not include a sufficient number of patients aged 65 years and older, therefore it is impossible to determine whether their response differs from that of younger subjects. Other reported clinical experience has not found differences in response between older and younger patients. Dosage selection should generally be cautious in older patients, as they are more likely to have impaired hepatic, renal, or cardiac function, as well as comorbidities or be receiving other medications.
Fatal medication errors have occurred due to confusion between calcium disodium EDTA (calcium EDTA) and disodium EDTA (discontinued in the US). Children and adults have been mistreated with disodium edetate instead of calcium disodium edetate; at least five deaths have been attributed to misuse of disodium edetate. Although both calcium disodium edetate and disodium edetate are heavy metal antagonists, they were initially approved by the U.S. Food and Drug Administration (FDA) for different purposes and with 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 lead to a significant drop in serum calcium levels, sometimes even fatal. In June 2008, after reviewing the risk-benefit ratio of the drug, the FDA withdrew its previous approval for disodium edetate due to safety concerns. The FDA stated at the time that it was not considering further action on calcium disodium edetate; most deaths due to the use of EDTA drugs involved medication errors, specifically the misuse of disodium edetate instead of calcium disodium edetate. The FDA has not received any reports of deaths due to the use of calcium disodium edetate. Disodium edetate injection is contraindicated in patients with anuria. It is not indicated for the treatment of age-related systemic arteriosclerosis. For more complete data on drug warnings for disodium edetate (22 in total), please visit the HSDB record page.

---

Pharmacodynamics
Anhydrous disodium edetate is a polyvalent ion chelator that lowers the concentration of calcium or digitalis in the blood. Because patients typically only need to take one dose daily, its duration of action is relatively long. The drug has a wide therapeutic index, and high doses are generally well tolerated. Patients should be informed of the risks of orthostatic hypotension, impaired myocardial contractility, hypokalemia, hypomagnesemia, and hypoglycemia.

C10H18N2NA2O10

372.24

372.075

6381-92-6

Ethylenediaminetetraacetic acid;60-00-4

636371

White to off-white solid powder

1.01 g/mL at 25 °C

>100 °C

250 °C (dec.)(lit.)

325.2ºC

n20/D 1.363

4

12

9

24

336

0

OVBJJZOQPCKUOR-UHFFFAOYSA-L

InChI=1S/C10H16N2O8.2Na.2H2O/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);;;2*1H2/q;2*+1;;/p-2

disodium;2-[2-[carboxylatomethyl(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetate;dihydrate

2934.99.9001

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.

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

H2O: 33.33 mg/mL (89.54 mM)
DMSO: < 1 mg/mL

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 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).

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)]
*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 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
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.)