Metabolic disposition of 14C-muroctasin in laboratory animals

Abstract 1. The absorption, distribution, metabolism and excretion of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a novel compound having an immunomodulator action, have been studied in mice, rats, rabbits and monkeys. 2. MDP-Lys(L18) was well transferred in the body from the administered site after subcutaneous infection of various doses in all animals. 3. Species differences were observed in the whole blood elimination half-life, the longest being in rabbits with ca. 3 h. The values of other species were less than 2 h. On the other hand, the AUC value was the highest in rabbits followed in decreasing order by monkeys, rats and mice. 4. After the subcutaneous infection of 14C-MDP-Lys(L18) (1 mg/head) to mice, the most organ levels of the radioactivity reached the maximum within 2 h. The level was the highest in liver. Tissue distribution pattern in rats was identical to that in mice. 5. The route of excretion of radioactivity was mainly via expired CO2 in all animals. The values were 40-50% of dose, irrespective of animal species. Excretion rate of the radioactivity in the urine was the highest in rabbits followed in decreasing order by rats, monkeys and mice. The fecal excretion of radioactivity varied from 1-12% of dose among the species. 6. The major urinary and fecal metabolites were lactic acid and MDP-Lys(L18), respectively. It was revealed that MDP-Lys(L18) was rapidly biotransformed to N-acetylmuramic acid, lactic acid and carbon dioxide, successively.