Mangafodipir trisodium injection, a new contrast medium for magnetic resonance imaging: in vitro metabolism and protein binding studies of the active component MnDPDP in human blood

Journal of Pharmaceutical and Biomedical Analysis
Kim G ToftTore Skotland

Abstract

The binding to human serum proteins of MnDPDP (manganese(II) dipyridoxyl diphosphate), the active component of the magnetic resonance imaging contrast medium mangafodipir trisodium injection (Teslascan) was studied in ultrafiltration experiments. Sera from three males and three females were incubated with 86 microM [14C]MnDPDP for 60 min at room temperature (20-23 degrees C), followed by centrifugation through filters with a cut-off of 30 kDa. Analysis of the filtrates and the initial incubation mixtures for manganese, by ICP-AES, and for DPDP and its dephosphorylated metabolites DPMP (dipyridoxyl monophosphate) and PLED (dipyridoxyl ethylenediamine diacetate) by liquid scintillation counting, showed a clear difference in protein binding of manganese and the ligands under these conditions. Only 2.2 +/- 1.8% (mean +/- S.E.; n = 6) of DPDP, DPMP and PLED were bound to protein, whereas 26.9 +/- 2.9% (mean +/- S.E.; n = 6) of manganese was bound to protein. No binding of DPDP, DPMP or PLED to blood cells was observed when whole blood, containing either heparin or EDTA as anticoagulant, was spiked with [14C]MnDPDP and the cell-free fraction and the lysed cell fraction analysed by liquid scintillation counting. The extent of protein ...Continue Reading

References

Aug 24, 1976·Biochimica Et Biophysica Acta·R A GibbonsH W Symonds
Nov 27, 1992·Journal of Medicinal Chemistry·T R BaileyD C Pevear
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Jun 18, 1985·Biochimica Et Biophysica Acta·A M Scheuhammer, M G Cherian

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Citations

Aug 10, 2000·Journal of Magnetic Resonance Imaging : JMRI·V M Runge
Jan 1, 1997·European Journal of Drug Metabolism and Pharmacokinetics·K G ToftT Skotland
May 30, 2001·Journal of Pharmaceutical and Biomedical Analysis·K G ToftT Skotland
Jul 25, 2019·Heart·Nick B SpathScott I K Semple
Dec 1, 2018·Contrast Media & Molecular Imaging·N B SpathS I Semple
Nov 18, 2020·European Heart Journal Cardiovascular Imaging·N B SpathS I Semple

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