Tissue distribution and general safety of MnDPDP in male beagle dogs, with or without total common bile duct obstruction

Abstract

Purpose: Evaluation of the tissue distribution of manganese (Mn) and general safety in normal and cholestatic male beagle dogs after i.v. administration of mangafodipir trisodium (MnDPDP, Teslascan). Material and Methods: Male beagle dogs, with or without surgical obstruction of the common bile duct, received a single i.v. bolus injection of saline (control), or MnDPDP at doses of 10 or 50 μmol/kg b.w. and were sacrificed 1 or 7 days after treatment. Tox-icity was assessed and tissue concentrations of Mn were measured. Results: Increased tissue Mn concentrations were found in all dogs treated with MnDPDP and were greatest in those with biliary obstruction. Although Mn concentrations decreased with time in most tissues in each of the treated groups, this was not the case for the brain and adrenal glands in dogs with total biliary obstruction in which further increases in Mn concentrations were seen at the later time point. This suggested a re-distribution of Mn from the major body depots such as the liver. There were no effects of MnDPDP on clinical sign/behaviour, organ weights, histomorphology or clinical biochemistry. Conclusion: These findings indicate that a single clinical dose of 5 μmol/kg MnDPDP is likely to be well tolerated in patients with cholestasis.