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Pharmacokinetics of an immunomodulator peptidoglycan monomer in mice after intravenous administration
B Ladesić1, S Perović, I Hrsak
1Department of Organic Chemistry and Biochemistry, Ruder Bosković Institute, Zagreb, Croatia.
Abstract:
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.
Insights
This study tracked 14C-PGM in mice, finding rapid urinary excretion and low blood levels within an hour. Peptidoglycan monomer (PGM) showed accumulation in the intestines and brain over six hours.
Area of Science:
- Pharmacokinetics and Metabolism
- Immunomodulation
- Bacterial Components
Background:
- Low molecular weight immunomodulators like peptidoglycan monomer (PGM) play a role in immune responses.
- Understanding the distribution and excretion of PGM is crucial for its therapeutic applications.
Purpose of the Study:
- To investigate the pharmacokinetic profile of 14C-labeled peptidoglycan monomer (14C-PGM) after intravenous administration in mice.
- To determine the excretion pathways and organ distribution of PGM and its metabolites.
Main Methods:
- Intravenous injection of 14C-PGM into mice.
- Measurement of radioactivity in urine, blood, plasma, and various organs (kidneys, liver, spleen, lungs, intestines, brain) at different time points (15 min to 6 h).
- Analysis of PGM and its metabolites in urine.
Main Results:
- Rapid excretion of 14C-PGM, with 80% found in urine within 1 hour (62% as unchanged PGM).
- Low levels of radioactivity in blood (around 2% at 1 hour, 0.5% at 6 hours).
- Variable organ distribution: decreased in kidneys, lungs, spleen; stable in liver after initial decrease; accumulation in intestines and brain over 6 hours.
Conclusions:
- 14C-PGM is rapidly excreted via urine, with minimal systemic circulation.
- Differential organ retention, particularly accumulation in the intestines and brain, suggests localized biological activity.
- These pharmacokinetic findings are important for understanding the diverse biological effects of low molecular weight bacterial peptidoglycans.