Chapter A30: Edetate Calcium Disodium (CaNa₂Edta)

INTRODUCTION

Edetate calcium disodium (CaNa₂EDTA) is a chelator that is primarily used for the management of patients with severe lead poisoning (blood lead concentrations >70 mcg/dL) in conjunction with dimercaprol (British anti-Lewisite {BAL}). Edetate calcium disodium was replaced by succimer for the treatment of patients with lead concentrations between 45 and 70 mcg/dL. In a clinical trial with much criticism, disodium EDTA (Na₂EDTA) reduced adverse cardiovascular outcomes in patients with a history of myocardial infarction.^3,22,36,41 We recommend against using this preparation (Na₂EDTA) for lead chelation because of the potential for life-threatening hypocalcemia.

HISTORY

Ethylenediaminetetraacetic acid (EDTA) was discovered and synthesized in the 1930s and approved by the US Food and Drug Administration (FDA) as a food additive in the 1940s. Investigations on CaNa₂EDTA for lead toxicity and for Na₂EDTA for the reversal of cardiovascular disease began in the 1950s.

PHARMACOLOGY

Chemistry

Edetate calcium disodium is an ionic, water-soluble compound with an anhydrous molecular weight of 374.27 Da. It is also referred to as calcium disodium versenate, calcium disodium EDTA, or calcium disodium ethylenediaminetetraacetic acid.

Mechanism of Action

Edetate calcium disodium belongs to the family of polyaminocarboxylic acids. Although it is capable of chelating many metals, its current use is almost exclusively in the management of lead poisoning. The term chelate has its origin in the Greek word chele, which means “claw,” implying an ability to tightly grasp the metal.⁵² Implicit in chelation is the formation of a ring-structured complex. When CaNa₂EDTA chelates lead, the calcium is displaced and the lead takes its place, forming a stable ring compound.³⁴ Bone is the primary source of lead chelated by CaNa₂EDTA. The blood lead concentration drops due to urinary elimination; however, once chelation is stopped, redistribution to soft tissues, including the brain, and then bone occurs.¹¹ Although zinc, iron, manganese, copper, and mercury are also capable of displacing calcium and forming a stable chelate, for a number of reasons, only the effect on zinc is clinically significant.

PHARMACOKINETICS AND PHARMACODYNAMICS

Edetate calcium disodium is a highly polar drug with a small volume of distribution (V_d) due to its polar nature and approximates that of the extracellular fluid compartment regardless of renal function.^29,34,42 In one study of 14 patients the V_d was 0.05 to 0.23 L/kg.⁴² Edetate calcium disodium appears to penetrate erythrocytes poorly,^2,29 and less than 5% of CaNa₂EDTA gains access to the spinal fluid.^29,34 Oral administration of CaNa₂EDTA is not practical because the bioavailability is less than 5%. The half-life ...