Plasma pharmacokinetics,tissue distribution and excretion of MnDPDP in the rat and dog after intravenous administration

Abstract

Purpose: To investigate distribution and excretion of mangafodipir (MnDPDP, Teslascan) in the rat and dog.

Material and Methods: Formulations of either ¹⁴C-MnDPDP or ⁵⁴MnDPDP were injected intravenously at near clinical doses in rats and dogs.

Results: The manganese (Mn) moiety is rapidly removed from plasma with an elimination half-life of less than 25 min in both species, reflecting a rapid distribution to the tissues and an early excretion. The plasma clearance of the DPDP moiety is slower than that of Mn and it appears to distribute into the extracellular fluid. Mn is distributed largely to the liver, pancreas and kidneys, and in pregnant rats, also to foetal liver and bones. No transplacental passage of DPDP could be detected. The metal is mainly excreted by the faecal route, with a small fraction eliminated early in the urine. DPDP is rapidly and essentially completely excreted in the urine, consistent with the glomerular filtration rate.

Conclusion: The ligand does not appear to facilitate the transport of Mn into any organ except the kidney for subsequent excretion, and it reduces distribution to the heart. The Mn is taken up by those organs indicated for MR imaging, primarily liver and pan-creas.