EDETATE CALCIUM DISODIUM (ETHYLENEDIAMINETETRAACETIC ACID, EDTA)
Ethylenediaminetetraacetic acid (Figure 57–2) is an efficient che-lator of many divalent and trivalent metals in vitro. To prevent potentially life-threatening depletion of calcium, the drug should be administered only as the calcium disodium salt.EDTA penetrates cell membranes relatively poorly and there-fore chelates extracellular metal ions much more effectively than intracellular ions.
The highly polar ionic character of EDTA limits its oral absorption. Moreover, oral administration may increase lead absorption from the gut. Consequently, EDTA should be admin-istered by intravenous infusion. In patients with normal renal function, EDTA is rapidly excreted by glomerular filtration, with 50% of an injected dose appearing in the urine within 1 hour. EDTA mobilizes lead from soft tissues, causing a marked increase in urinary lead excretion and a corresponding decline in blood lead concentration. In patients with renal insufficiency, excretion of the drug—and its metal-mobilizing effects—may be delayed.
Edetate calcium disodium is indicated chiefly for the chelation of lead, but it may also have usefulness in poisoning by zinc, manga-nese, and certain heavy radionuclides. In spite of repeated claims in the alternative medicine literature, EDTA has no demonstrated use-fulness in the treatment of atherosclerotic cardiovascular disease.
Because the drug and the mobilized metals are excreted via the urine, the drug is relatively contraindicated in anuric patients. In such instances, the use of low doses of EDTA in combination with high-flux hemodialysis or hemofiltration has been described. Nephrotoxicity from EDTA has been reported, but in most cases can be prevented by maintenance of adequate urine flow, avoid-ance of excessive doses, and limitation of a treatment course to5 or fewer consecutive days. EDTA may result in temporary zinc depletion that is of uncertain clinical significance. Analogs of EDTA, the calcium and zinc disodium salts of DTPA, pentetate, have been used for removal (“decorporation”) of certain tran-suranic, rare earth, and transition metal radioisotopes, and in 2004 were approved by the FDA for treatment of contamination with plutonium, americium, and curium.