General toxicology of MnDPDP.
OBJECTIVE
To investigate the general toxicology of mangafodipir trisodium (MnDPDP, Teslascan).


METHODS
Studies were performed in accordance with standard methods and in compliance with regulations current at the time of conduct.


RESULTS
Single-dose studies in rodents and dogs showed that MnDPDP was tolerated at doses of approximately 2000 mumol/kg, approximately 400 times a single imaging dose of 5 mumol/kg. The single dose tolerance of MnDPDP was approximately 10 times greater than MnCl2. A good safety profile of MnDPDP was also shown in repeat-dose studies (3 weeks), in which the no-observed-adverse-effect level for the rat, monkey and dog was 116, 29 and 10 mumol/kg, respectively. The local tolerance studies indicated that no adverse local tissue reactions are likely to occur after i.v. injection. Other studies indicate that accidental spillage of MnDPDP onto the skin is not expected to lead to significant systemic exposure, or to local irritation or hypersensitivity. MnDPDP was not genotoxic in a battery of several different tests.


CONCLUSIONS
MnDPDP was shown to have a good safety profile suitable as an hepatobiliary MR contrast agent for i.v. administration.
Larsen
L E
LE
Nycomed Imaging AS, Oslo, Norway.
Grant
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D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D008297:Male; D008345:Manganese / Q000276:immunology / Q000493:pharmacokinetics; D020149:Manganese Poisoning; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity; D012869:Skin Absorption / Q000187:drug effects
D003287:Contrast Media; D008345:Manganese; D011732:Pyridoxal Phosphate; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid