Metabolism of mangafodipir trisodium (MnDPDP), a new contrast medium for magnetic resonance imaging, in beagle dogs

Summary

The metabolism of MnDPDP (manganese(II)N,N′-dipyridoxylethylenediamine-N,N′-diacetate-5,5′-bis(phosphate) was studied in dogs after intravenous infusion for 12.5 min with either 10, 30 or 100 μmol MnDPDP/kg b.w. HPLC analyses of plasma samples obtained 1, 5 and 30 min after the end of infusion revealed that MnDPDP was rapidly dephosphorylated to MnDPMP (manganese(II)N,N′-dipyridoxylethylenediamine-N,N′-diacetate-5-phosphate) and MnPLED (manganese(II)N,N′-dipyridoxylethylenediamine-N,N′-diacetate), with simultaneous transmetallation to the corresponding zinc metabolites ZnDPDP, ZnDPMP and ZnPLED. In the low-dose group, the parent compound MnDPDP was present at the lowest concentration compared to the metabolites at the first sampling time point, 1 min after the end of infusion, whereas MnPLED was the main metabolite. At 30 min post-infusion ZnPLED was the main metabolite. The medium- and high-dose groups showed a similar metabolic pattern. In the high-dose group, MnPLED was the main metabolite at all sampling time points. The estimated plasma half-life of total ligand was 20 min, and it was dose-independent with an apparent volume of distribution of 0.2 l/kg. The rate of dephosphorylation was similar to the rate of transmetallation, and both were dose-independent. However, calculations of the total Mn and Zn ligands indicated that the apparent plasma elimination was dose-dependant. The half-life for total Mn ligands which is a combination of both metabolism and elimination, were 10 and 20 min at 10 and 100 μmol/kg, respectively. The half-life for total Zn ligands which is the half-life for rate of formation of Zn ligands, were 40 and 65 min at 10 and 100 μmol/kg, respectively. No sex differences in metabolic pattern were observed in any of the three dosage groups.