Calcium disodium edetate hydrate (EDTA disodium calcium salt hydrate; Ethylenediaminetetraacetic acid disodium calcium salt hydrate)   中文名称: 乙二胺四乙酸钙二钠盐

Absorption, Distribution and Excretion
Calcium edetate disodium's Cmax and AUC are dependant on renal function. 5% of an oral dose is absorbed from the gastrointestinal tract.
Edetate calcium disodium is 95% eliminated in the urine within 24 hours. An oral dose in rats was 88.32% recovered in the feces and 10.30% recovered in the urine.
The volume of distribution of edetate calcium disodium is 0.19±0.10L/kg.
The mean clearance of edetate in 1 month olds is 54.6mL/min/1.73m². 2-17 year olds have a mean clearance of 113.9±24.4mL/min/1.73m².
Edetate calcium disodium is poorly absorbed from the gastrointestinal tract.
Edetate calcium disodium is well absorbed following IM or subcutaneous administration. When edetate calcium disodium is administered IV in the treatment of lead poisoning, urinary excretion of chelated lead begins within about 1 hour and peak excretion of chelated lead occurs within 24-48 hours. Colic caused by lead poisoning may disappear within 2 hours, muscular weakness and tremors disappear after 4-5 days, and coproporphyrinuria and stippled erythrocytes usually decrease within 4-9 days after therapy is initiated.
Edetate calcium disodium is distributed mainly into extracellular fluid. The drug does not penetrate erythrocytes...
Following parenteral administration, it is rapidly excreted by glomerular filtration in urine, either unchanged or as metal chelates. Following IV administration, 50% of a dose appears in urine within 1 hour and 95% within 24 hours. ... Changes in urine flow and/or pH do not affect the excretion rate of edetate calcium disodium, but impaired renal function with reduced glomerular filtration delays excretion of the drug and thus may increase its nephrotoxicity.
For more Absorption, Distribution and Excretion (Complete) data for DISODIUM CALCIUM EDTA (10 total), please visit the HSDB record page.

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Metabolism / Metabolites
Edetate calcium disodium is almost completely unmetabolized _in vivo_.
Edetate calcium disodium is not metabolized.

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Biological Half-Life
The half life of edetate calcium disodium is 20-60 minutes.
The plasma half-life of the drug has been reported to be 20-60 minutes following IV administration and 1.5 hours following IM administration.

Interactions
Zinc supplements (concurrent use may decrease the effectiveness of edetate calcium disodium and zinc supplements due to chelation; zinc supplement therapy should be withheld until edetate calcium disodium therapy is completed)
Edetate calcium disodium interferes with the action of zinc insulin preparations by chelating the zinc.
Concomitant administration of CaNa2EDTA and dimercaprol (BAL) increases the rate of lead mobilization from tissue depots and probably reduces the incidence of central nervous system toxicity when compared with the single use of CaNa2EDTA.
Steroids enhance the renal toxicity of edetate calcium disodium in animals.

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Non-Human Toxicity Values
LD50 Rat oral 10 g/kg
LD50 Rat ip 3.85 g/kg
LD50 Rat iv 3 g/kg
LD50 Mouse ip 4.5 g/kg
For more Non-Human Toxicity Values (Complete) data for DISODIUM CALCIUM EDTA (6 total), please visit the HSDB record page.

EDTA monocalcium diisodium salt is an organic calcium salt of EDTA diisodium. It is a chelating agent that is used for the treatment of lead poisoning. It has a role as a geroprotector, a chelator and an antidote. It contains an EDTA disodium salt (anhydrous).
Edetate calcium disodium is a metal ion chelator used to reduce blood concentrations and depot stores of lead from the body. It is on the World Health Organization Model List of Essential Medicines. Edetate calcium disodium was granted FDA approval on 16 July 1953.
Edetate Calcium Disodium is contracted name for a salt of ethylenediaminetetraacetate, an agent used as a chelator of lead and some other heavy metals. C10H12CaN2Na2O8.
A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.

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Drug Indication
Edetate calcium disodium is indicated to reduce blood levels and depot stores of lead in acute and chronic lead poisoning.

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Mechanism of Action
Edetate calcium disodium distributes into tissues, such as the kidney and bone, where it chelates lead ions. The lead ions are then eliminated in the normal urinary excretion of edetate. Lead in certain tissues such as the liver and bone, redistribute to other tissues after edetate calcium disodium treatment, but lead levels do not decrease to levels seen in unexposed patients.
The calcium in edetate calcium disodium can be displaced by divalent and trivalent metals, particularly lead, to form stable soluble complexes that can then be excreted in urine. Unlike edetate disodium (no longer commercially available in the US), edetate calcium disodium is saturated with calcium and therefore can be administered IV in relatively large quantities without causing any substantial changes in serum or total body calcium concentrations. Although 1 g of edetate calcium disodium theoretically sequesters 620 mg of lead, an average of only 3-5 mg of lead is excreted in urine following parenteral administration of 1 g of the drug to patients with symptoms of acute lead poisoning or with high concentrations of lead in soft tissues.
Parenteral administration of edetate calcium disodium chelates and greatly increases the urinary excretion of zinc and, to a much lesser extent, cadmium, manganese, iron, and copper. Excretion of uranium, plutonium, yttrium, and some other heavier radioactive isotopes can be increased to a limited extent by edetate calcium disodium chelation. Although mercury readily displaces calcium from edetate calcium disodium in vitro, patients with mercury poisoning do not respond to the drug.
The pharmacologic effects of edetate calcium disodium are due to the formation of chelates with divalent and trivalent metals. A stable chelate will form with any metal that has the ability to displace calcium from the molecule, a feature shared by lead, zinc, cadmium, manganese, iron and mercury. The amounts of manganese and iron mobilized are not significant. Copper is not mobilized and mercury is unavailable for chelation because it is too tightly bound to body ligands or it is stored in inaccessible body compartments. The excretion of calcium by the body is not increased following intravenous administration of edetate calcium disodium, but the excretion of zinc is considerably increased.
The primary source of lead chelated by calcium disodium edetate is from bone; subsequently, soft-tissue lead is redistributed to bone when chelation is stopped. There is also some reduction in kidney lead levels following chelation therapy.
For more Mechanism of Action (Complete) data for DISODIUM CALCIUM EDTA (6 total), please visit the HSDB record page.

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Therapeutic Uses
Edetate calcium disodium is indicated for the reduction of blood levels and depot stores of lead in lead poisoning (acute and chronic) and lead encephalopathy, in both pediatric populations and adults. Chelation therapy should not replace effective measures to eliminate or reduce further exposure to lead. /Included in US product label/
The US Food and Drug Administration (FDA) states that the safety and effectiveness of edetate calcium disodium for use in removing heavy metals (eg, mercury) and toxins from the body, management of coronary artery disease, or other uses not described in the manufacturer's labeling have not been established.
VET: Chelating agent in lead poisoning.
/SRP: Former use/ EDTA lead-mobilization test has proved to be a sensitive indicator of excessive body stores of lead. This test was used to evaluate cumulative past lead absorption in 48 men diagnosed as having essential hypertension, a disease considered a possible complication of lead poisoning.
For more Therapeutic Uses (Complete) data for DISODIUM CALCIUM EDTA (8 total), please visit the HSDB record page.

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Drug Warnings
/BOXED WARNING/ WARNINGS: Calcium Disodium Versenate is capable of producing toxic effects which can be fatal. Lead encephalopathy is relatively rare in adults, but occurs more often in pediatric patients in whom it may be incipient and thus overlooked. The mortality rate in pediatric patients has been high. Patients with lead encephalopathy and cerebral edema may experience a lethal increase in intracranial pressure following, intravenous infusion; the intramuscular route is preferred for these patients. In cases where the intravenous route is necessary, avoid rapid infusion. The dosage schedule should be followed and at no time should the recommended daily dose be exceeded.
Fatal medication errors have occurred that involve confusion between edetate calcium disodium (calcium EDTA) and edetate disodium (no longer commercially available in the US). Children and adults have mistakenly received edetate disodium instead of edetate calcium disodium; at least 5 deaths have occurred as a result of inadvertent administration of edetate disodium. Although both edetate calcium disodium and edetate disodium are heavy metal antagonists, the 2 drugs were originally approved by the US Food and Drug Administration (FDA) for different uses and have different effects; edetate disodium was formerly FDA approved for use in selected patients for the emergency treatment of hypercalcemia or for the control of ventricular arrhythmias associated with cardiac glycoside toxicity. Use of edetate disodium may result in a substantial, and sometimes fatal, decrease in serum calcium concentrations. In June 2008, FDA withdrew its prior approval for edetate disodium because of safety concerns following a review of the risk-benefit profile of the drug. FDA stated that it was not considering additional action regarding edetate calcium disodium at that time; most of the fatalities following administration of an EDTA drug have involved medication errors in which edetate disodium was administered instead of edetate calcium disodium. FDA has not received reports of any fatalities resulting from the administration of edetate calcium disodium that involve a medication error.
The manufacturer states that the drug is contraindicated in patients with anuria and in those with active renal disease. Edetate calcium disodium also is contraindicated in patients with hepatitis.
The principal and most serious toxic effect of edetate calcium disodium is renal tubular necrosis, which tends to occur when the daily dose is excessive and may result in fatal nephrosis. Edetate calcium disodium may produce the same signs of renal damage as lead poisoning, such as proteinuria and microscopic hematuria. Rarely, changes in distal renal tubules and glomeruli, glycosuria, presence of large renal epithelial cells in urinary sediment, increased urinary frequency, and urgency may occur. Hydropic degeneration of proximal renal tubular cells also may occur; however, recovery usually occurs following discontinuance of therapy.
For more Drug Warnings (Complete) data for DISODIUM CALCIUM EDTA (24 total), please visit the HSDB record page.

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Pharmacodynamics
Edetate calcium disodium is a polyvalent ion chelator used to remove lead from the body after lead poisoning. It has a wide therapeutic index, as overdoses must be well in excess of the therapeutic dose to show symptoms. It has a long duration of action, as doses are given at least a day apart. Patients should be counselled regarding the risk of increased intracranial pressure with intravenous infusions.

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

167

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

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。