title: Metabolism and pharmacokinetics of MnDPDP in man.
abstract: 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.
authors.affiliation: Nycomed Imaging AS, Oslo, Norway. ktt@nycomed.com
authors.forename: K G
authors.initials: KG
authors.lastname: Toft
authors.forename: S O
authors.initials: SO
authors.lastname: Hustvedt
authors.forename: D
authors.initials: D
authors.lastname: Grant
authors.forename: I
authors.initials: I
authors.lastname: Martinsen
authors.forename: P B
authors.initials: PB
authors.lastname: Gordon
authors.forename: G A
authors.initials: GA
authors.lastname: Friisk
authors.forename: A J
authors.initials: AJ
authors.lastname: Korsmo
authors.forename: T
authors.initials: T
authors.lastname: Skotland
mesh_terms: 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
chemical_list: D003287:Contrast Media; D008345:Manganese; D011732:Pyridoxal Phosphate; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid