Optimizing Ca-DTPA/Zn-DTPA therapy for internal decorporation: transitioning from intravenous to oral route with insights on safety and toxicity.

Abstract

Ca-DTPA and Zn-DTPA are the decorporating agents approved by the USFDA for removing plutonium, americium, or curium from the subjects known or suspected to be contaminated with these radionuclides. Ca-DTPA and Zn-DTPA are well-known chelating agents with a strong affinity for many bivalent, trivalent, and certain tetravalent metal ions, including plutonium (Pu⁺⁴) and thorium (Th⁺⁴). The major problem associated with Ca-DTPA and Zn-DTPA therapy is that the only approved route of administration is intravenous or inhalation due to its extremely poor bioavailability. Both these drugs belong to BCS class III drugs with high solubility and low permeability. Researchers are exploring various approaches to make these drugs bioavailable via alternate routes, especially the oral route. This will enable pre-hospital care, better patient compliance, and minimize its clinically significant side effect of electrolyte imbalance. The present paper highlights the practical feasibility and challenges of establishing an oral route for delivering Ca-DTPA and Zn-DTPA with the research around it. Also, the paper highlights the importance of establishing an oral dose and the dosing schedule for Ca-DTPA and Zn-DTPA before plunging into its formulation development. These advancements underline the potential of orally administered chelating agents and alternative delivery methods in addressing the limitations of current intravenous formulations and improving accessibility and patient outcomes.