PLASMA PHARMACOKINETICS, TISSUE DISTRIBUTION AND EXCRETION OF MNDPDP IN THE RAT AND DOG AFTER INTRAVENOUS ADMINISTRATION

Purpose: To investigate distribution and excretion of mangafodipir (Mn DPDP, Teslascan) in the rat and dog. Material and Methods: Formulation s of either C-14-MnDPDP or (MnDPDP)-Mn-54 were injected intravenously at near clinical doses in rats and dogs. Results. The manganese (Mn) m oiety is rapidly removed from plasma with an elimination half-life of less than 25 min in both species, reflecting a rapid distribution to t he tissues and an early excretion. The plasma clearance of the DPDP mo iety is slower than that of Mn and it appears to distribute into the e xtracellular fluid. Mn is distributed largely to the liver, pancreas a nd kidneys, and in pregnant rats, also to foetal liver and bones. No t ransplacental passage of DPDP could be detected. The metal is mainly e xcreted 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: Th e ligand does not appear to facilitate the transport of Mn into any or gan except the kidney for subsequent excretion, and it reduces distrib ution to the heart. The Mn is taken up by those organs indicated for M R imaging, primarily liver and pancreas.