Plasma pharmacokinetics, tissue distribution and excretion of MnDPDP in the rat and dog after intravenous administration.
OBJECTIVE
To investigate distribution and excretion of mangafodipir (MnDPDP, Teslascan) in the rat and dog.


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.


CONCLUSIONS
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 pancreas.
Hustvedt
S O
SO
Nycomed Imaging AS, Oslo, Norway. sohu@nycomed.com
Grant
D
D
Southon
T E
TE
Zech
K
K
D000818:Animals; D002250:Carbon Radioisotopes; D003287:Contrast Media / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D004285:Dogs; D004492:Edetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D008024:Ligands; D008297:Male; D008345:Manganese / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D011247:Pregnancy; D011732:Pyridoxal Phosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D011868:Radioisotopes; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution; D014915:Whole-Body Counting
D002250:Carbon Radioisotopes; D003287:Contrast Media; D008024:Ligands; D011868:Radioisotopes; D008345:Manganese; D011732:Pyridoxal Phosphate; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid