Pharmacokinetics and Metabolism of Muramyl Dipeptide and Nor-muramyl Dipeptide [3H-labelled] in the Mouse

The fates of 3H-muramyl dipeptide (MDP) and 3H-nor-MDP have been investigated after intravenous (i.v.), intraperitoneal, and subcutaneous injection of a range of doses in the mouse. After i.v. injection both compounds were cleared rapidly from the circulation, distributed initially to the tissues, and finally excreted largely intact in the urine. Most of the tissues contained intact material at 2 min after injection, but the much lower levels of radioactivity persisting at 1 h had undergone considerable metabolism (except in intestine, where some intact material persisted for as long as 24 h). Some accumulation of radioactivity was observed in liver and kidney and there were quantitative and qualitative differences between the two compounds. Characterisation of some of the metabolites in these tissues was undertaken, and the deamidated muramyl dipeptide was tentatively identified which is known to have some biological activity. The mechanism of the biological effects, which may be expressed over a relatively long time period, remains to be explained in view of the rapid excretion of most of the dose.