engleski

Metabolic fate of novel adamantyltripeptides in mice after intravenous administration

The major aim of the present study was to investigate the metabolic fate and distribution of adamantyltripeptides, previously shown to be potential immunomodulators and antimetastatic agents. To facilitate the study of metabolic fate of adamantyltripeptide isomers the D-(adamant-2-yl)-glycyl-L-(U-14C)-alanyl-D-isoglutamine(14C-AdTP1)and L--(adamant-2-yl)-glycyl-L-(U-14C)-alanyl-D-isoglutamine(14C-AdTP2)were synthesized by use of uniformly labelled L-alanine. The distribution of water soluble adamantyltripeptide isomers in blood and in some organs (lungs, liver, spleen, brain and kidneys) was determined at different time intervals within the period of 1-48 hrs following i.v. administration in mice. Simultaneously, excretion of radioactivity in urine was observed and excreted 14C-labelled adamantyltripeptide isomers were characterised. Two isomeres of adamantyltripeptides showed a different pattern in excretion and tissue distribution in mice. The excretion of 14C-AdTP2 in urine was slower than that of 14C-AdTP1. Retention of adamantyltripeptide isomeres in blood was similar. Both isomeres were retained mostly in the liver, 14C-AdTP2 more than 14C-AdTP1 at later time intervals. It should be stressed that 14C-AdTP2 was always found in higher amount than 14C-AdTP1 in the brain at all studied time intervals.

adamantyltripeptides; distribution; excretion

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