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

European Journal of Drug Metabolism and Pharmacokinetics
K G ToftT Skotland

Abstract

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 mumol 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 metabolic. 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 transmetal...Continue Reading

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