Disodium Edetate Dihydrate: Pharmacokinetics, Mechanism of Action and Side Effects

General Description

Disodium edetate dihydrate, a pharmaceutical compound, exhibits poor gastrointestinal absorption, distributes to various organs, and is primarily eliminated through urine and feces unchanged. Its mechanism of action involves chelating polyvalent ions like calcium, magnesium, and zinc, reducing their blood concentrations. This chelation process can lower serum calcium levels, affect myocardial contractility, and increase urinary excretion of certain metals. While generally well-tolerated, potential side effects include renal irritation. Monitoring for adverse effects is crucial. Overall, Disodium edetate dihydrate acts as a polyvalent ion chelator with therapeutic benefits but requires careful consideration and monitoring for potential side effects.

Figure 1. Disodium edetate dihydrate

Pharmacokinetics

Disodium edetate dihydrate, also known as disodium EDTA, is a pharmaceutical compound used as an excipient in various preparations. Its pharmacokinetics involve absorption, distribution, and elimination processes. When taken orally, Disodium edetate dihydrate is poorly absorbed from the gastrointestinal tract, with only 5.3% of the dose recovered in urine and 88.5% in feces in rat studies. The volume of distribution of disodium edetate anhydrous is not readily available. Disodium edetate dihydrate distributes to several organs such as the liver, small intestine, large intestine, and kidneys. Intravenous administration leads to 95% of the dose being excreted in urine within 24 hours, with 50% appearing within the first hour. A small percentage of the dose (5.3%) is excreted in urine, and a larger percentage (88.5%) in feces after oral administration in rats. Disodium edetate dihydrate is almost completely unmetabolized in the body, suggesting no significant metabolic transformations. The chelate formed by disodium edetate is excreted in urine, with 50% excreted within the first hour and over 95% within 24 hours, indicating a relatively short biological half-life. Overall, disodium edetate dihydrate exhibits poor gastrointestinal absorption, distributes to various organs, and is primarily eliminated through urine and feces, remaining largely unchanged in the body. ¹

Mechanism of Action

The mechanism of action of disodium edetate dihydrate involves its ability to chelate polyvalent ions, such as calcium, magnesium, zinc, and other divalent and trivalent metals. This chelation process allows disodium edetate to form complexes with these ions, leading to their reduced concentrations in the blood. When administered as an injection, disodium edetate dihydrate can lower serum calcium levels due to its strong affinity for calcium ions. This effect occurs during intravenous infusion and can be further enhanced with prolonged infusion, which may mobilize calcium from extracirculatory stores. Additionally, disodium edetate dihydrate exerts a negative inotropic effect on the heart, affecting myocardial contractility. Apart from calcium, disodium edetate dihydrate can also form chelates with magnesium, zinc, and other trace elements, leading to increased urinary excretion of these metals. However, disodium edetate dihydrate does not form a chelate with potassium, although it may reduce serum potassium levels and increase urinary potassium loss. Due to its chelating properties, disodium edetate is used to reduce blood concentrations of calcium or digitalis. It has a long duration of action, often requiring a daily dose. The therapeutic index is wide, as high doses are generally well tolerated. However, patients should be informed about potential side effects such as postural hypotension, negative effects on myocardial contractility, as well as the risk of hypokalemia, hypomagnesemia, and hypoglycemia. In summary, disodium edetate dihydrate acts as a polyvalent ion chelator, reducing concentrations of calcium and other divalent and trivalent metals in the blood through the formation of chelate complexes. Its mechanism of action includes lowering serum calcium levels, negative inotropic effects on the heart, and increased urinary excretion of magnesium, zinc, and other trace elements. ²

Side Effects

Disodium edetate dihydrate may have some side effects. In a study involving patients treated for acrosclerosis with intravenous Disodium edetate dihydrate, one patient experienced renal irritation characterized by albuminuria and granular casts. However, this side effect resolved completely upon discontinuation of the drug. It's worth noting that this patient received Disodium edetate dihydrate over a shorter period than the other patients in the study. Another study evaluated the irritancy potential of Disodium edetate dihydrate using a patch test. None of the 26 volunteers treated with Disodium EDTA experienced any irritation, unlike the volunteers treated with sodium dodecyl sulfate, where 21 out of 26 individuals exhibited irritancy. In a separate study, Disodium edetate dihydrate was administered intravenously in 5-day courses over a 15-month period to patients with severe, noncalcific acrosclerosis. The side effects were minimal and did not require discontinuation of therapy. Patients experienced subjective and objective softening of the skin, with microscopic examination revealing improvements such as increased vascularity, return of fixed tissue cells, and loosening of collagen bundles. Overall, while Disodium edetate dihydrate appears to have a favorable safety profile, it is important to monitor patients for potential side effects such as renal irritation. As with any medication, it is advisable to consult with a healthcare professional for personalized information and guidance regarding the use of Disodium edetate dihydrate. ¹

Reference

1. Edetate Disodium. National Center for Biotechnology Information. 2024; PubChem Compound Summary for CID 636371.

2. Edetate disodium anhydrous. DrugBank. DB14600.