Metabolism and pharmacokinetics of MnDPDP in man.
OBJECTIVE
To study the metabolism and pharmacokinetics of mangafodipir trisodium injection, 0.01 mmol/ml (Teslascan), in healthy male volunteers.


METHODS
Eight volunteers received mangafodipir trisodium as an infusion over 20 min, and 5 received it as an injection (< 1 min). Both groups received 5 and 10 mumol/kg b.w. with a wash-out period of 3 weeks between doses. Metabolites were measured in plasma, total manganese and zinc were measured in plasma and urine and total manganese was measured in faeces.


RESULTS
The parent compound MnDPDP (manganese dipyridoxyl diphosphate) and 5 metabolites; MnDPMP (manganese dipyridoxyl monophosphate). MnPLED (manganese dipyridoxyl ethylenediamine) and the corresponding zinc compounds ZnDPDP, ZnDPMP and ZnPLED, were detected in plasma. ZnPLED was the only detectable metabolite 8 h after dosing. The apparent volume of distribution of manganese exceeded the interstitial body fluids. The volume of distribution of the ligand indicated distribution to the extracellular fluid only, with the plasma clearance close to the glomerular filtration rate. The manganese was incompletely excreted during the 4 days after treatment with the major part in faeces and less than 20% of the dose in the urine.


CONCLUSIONS
Dephosphorylation and simultaneous transmetallation with zinc are the main metabolic pathways of MnDPDP in man.
Toft
K G
KG
Nycomed Imaging AS, Oslo, Norway. ktt@nycomed.com
Hustvedt
S O
SO
Grant
D
D
Martinsen
I
I
Gordon
P B
PB
Friisk
G A
GA
Korsmo
A J
AJ
Skotland
T
T
D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000706:statistics & numerical data; D003287:Contrast Media / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics; D005243:Feces / Q000737:chemistry; D006801:Humans; D008297:Male; D008345:Manganese / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics*; D011732:Pyridoxal Phosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics; D012016:Reference Values; D013997:Time Factors
D003287:Contrast Media; D008345:Manganese; D011732:Pyridoxal Phosphate; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid