Pharmacokinetics of an immunomodulator peptidoglycan monomer in mice after intravenous administration.
A 14C labeled low molecular weight immunomodulator, peptidoglycan monomer (14C-PGM), was injected intravenously (i.v.) into mice. At various time intervals thereafter (15 min-6 h), radioactivity in the urine, whole blood, plasma, kidneys, liver, spleen, lungs, intestines and the brain of the mice was determined. Shortly after injection, 14C-PGM was very rapidly excreted from the organism, so that 1 h following administration, 80% of the radioactivity was found in the urine (62% as unchanged PGM and the rest as the metabolites pentapeptide and disaccharide). At the same time, around 2% of the injected material was found in the blood. Six hours after injection, equal quantities were found in the intestines, liver and blood (0.5%), slightly less in the kidneys, lungs and spleen (0.2-0.3%) and the least quantity in the brain (0.04%). However, the dynamics of retention in the organs was evidently different. In the kidneys, lungs and spleen, radioactivity steadily decreased over the studied period. In the liver following an initial decrease, radioactivity remained the same 3 and 6 h after injection. On the other hand, in the intestines and brain PGM seemed to accumulate rather than disappear following i.v. administration. This fact should be considered when explaining different biological activities of low molecular weight bacterial peptidoglycans.
Ladesić
B
B
Department of Organic Chemistry and Biochemistry, Ruder Bosković Institute, Zagreb, Croatia.
Perović
S
S
Hrsak
I
I
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000595:Amino Acid Sequence; D000818:Animals; D002240:Carbohydrate Sequence; D005260:Female; D007275:Injections, Intravenous; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010457:Peptidoglycan; D014018:Tissue Distribution
D000276:Adjuvants, Immunologic; D010457:Peptidoglycan; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C032972:peptidoglycan pentapeptide-mDap3