engleski

Pharmacokinetics of 14C-labelled adamantyltripeptides in mice

As previously reported (1), novel type of compounds, adamantyltripeptides, that contain peptides specific for bacterial peptidoglycans (immunomodulatory activity) and an adamantyl residue (antiviral activity) have been successfully synthesized. The major aim of the present study was to investigate the pharmacokinetic profile of adamantyltripeptides in the mammalian organism. It was necessary, therefore, to prepare radioactively labelled 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). The adamantyltripeptides were synthesized by use of uniformely labelled L-alanine. The distribution of radiactivity originating from water soluble adamantyltripeptide isomers in blood and in some major organs (lungs, liver, speen, brain and kidneys) was determined at different time intervals within the period of 1-48 h, following i.v. administration in mice. Simultaneously, the excretion of radioactivity in urine was followed and excreted 14C-labelled adamantyltripeptide isomers were characterized. Isomers of adamantyltripeptide showed a different pattern in excretion and tissue distribution in mice. Both isomers were retained mostly in the liver, 14C-AdTP2 more than 14C-AdTP1 at later time intervals. Excretion of 14C-AdTP2 in urime and blood was slower than that of 14C-AdTP1. 1 Vranešić et al. Helv. Chim. Acta 76 (1993) 1752

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