METABOLISM AND PHARMACOKINETICS OF MNDPDP IN MAN

Purpose: To study the metabolism and pharmacokinetics of mangafodipir trisodium injection, 0.01 mmol/ml (Teslascan), in healthy male volunte ers. Material and Methods: Eight volunteers received mangafodipir tris odium as an infusion over 20 min, and 5 received it as an injection (< 1 min). Both groups received 5 and 10 mu mol/kg b.w. with a wash-out p eriod of 3 weeks between doses. Metabolites were measured in plasma, t otal manganese and zinc were measured in plasma and urine and total ma nganese was measured in faeces. Results: The parent compound MnDPDP (m anganese dipyridoxyl diphosphate) and 5 metabolites; MnDPMP (manganese dipyridoxyl monophosphate), MnPLED (manganese dipyridoxyl ethylenedia mine) 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 exceed ed the interstitial body fluids. The volume of distribution of the lig and indicated distribution to the extracellular fluid only, with the p lasma 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. Concl usion: Dephosphorylation and simultaneous transmetallation with zinc a re the main metabolic pathways of MnDPDP in man.