Investigations into the metabolic fate and distribution of hepzidine maleate in the rat and the mouse.

摘要: Abstract Metabolic studies with hepzidine maleate, labelled in two positions 3H and 14C, respectively, showed that rats, over 50 per cent of an orally administered dose maleate (10 mg kg ) is hydrolysed before absorption. The nonhydrolysed part the absorbed to a large extent. An important biotransformation N-demethylation; it involves about 20 10- oral 37 equal dose, given i.p. On other hand, N-demethylation hydrolytic product 1-methyl-4-piperidinol was very slight. Excretion 14C radioactivity expired air shows good first-order kinetics, from which half-life 4.2 hr could be evaluated for rat. Next urinary excretion, biliary excretion plays role elimination metabolites. In urine products hepzidine, especially its metabolites (probably conjugates) are predominant. There evidence bile 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ol predominant, but contrast substantial amount excreted as such and/or some form still possesses intact structure. After administration maleate-14C female mice (50 autoradiographic distribution show attain considerable levels most organs, while blood stay relatively low. Highest accumulations found liver, lungs, hypophysis, Harder's gland, submaxillary mucous glands tongue, palatum pharynx, bone marrow, lymphoid tissue, bladder wall, urine, bile, intestinal contents, specified zones kidneys adrenals. To lesser degree there also pronounced penetration into CNS, where hippocampus, cerebral cortex thalamus higher than brain areas. organs maximum observed at 1 after administration. No specific long-lasting have been observed, except high level 16