The Combined Use of Leutragin and Pulmonary Surfactant-BL Increases Animal Survival in a Model of Fatal Acute Respiratory Distress Syndrome

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This paper presents a study into the pharmacokinetics of a new inhaled anti-inflammatory hexapeptide, registered as “Leutragin”. This drug is used as a new treatment approach for viral pneumonias, whose severe course is directly related to the cytokine inflammatory cascade referred to as a cytokine storm. The study involved investigation of lung tissue and serum after a single inhalation administration of Leutragin to mice of the C57BL/6Y line at a dose of 150 mg/kg. The time required to reach the maximum concentration (Tmax) of Leutragin in serum and lung was 30 min and 10 min, respectively. The maximum concentration (Cmax) in lung was 358.5 ng/g, which exceeded the concentration maximum for blood (53.84 ng/g) by over six times. It was found that, after inhalation administration, Leutragin is rather rapidly eliminated from the body with the half-life of the drug (t1/2el) from blood serum and lungs ranging from 25.8 to 38.9 min.

Comparative Pharmacokinetics Study of the Leutragin Peptide Drug in Blood Serum and Lung Tissue in C57BL/6Y Mice after Single Inhalation Administration

Ogneva,

Nesterov,

Khvostov

et al. 2024

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Comparative Pharmacokinetics Study of the Leutragin Peptide Drug in Svetlogorsk Minipig Blood Serum after Single Administration

Ogneva,

Nesterov,

Khvostov

et al. 2024

In this work, we investigate the pharmacokinetics of a new anti-inflammatory hexapeptide registered under the name of Leutragin. The study was conducted on Svetlogorsk minipigs by intravenous and a single rectal administration of the drug in the form of a solution and suppositories at an equal dose of 10 mg. The shortest time to reach peak concentration was demonstrated with intravenous administration, with the Tmax being 30 min. The maximum concentration (Cmax) when administering Leutragin in a suppository form was 141.37 ng/g. This concentration was achieved at the Tmax of 90 min, following which Leutragin remained in the bloodstream for 2.5 h. The absolute bioavailability of Leutragin in the suppository and solution form was 59.6% and 70.03%, respectively. The peak concentration of Leutragin under its rectal administration occurred at 150 min, following with the drug remained in the bloodstream for 4 h.

Cytological analysis of the lung material of C57BL/6Y mice in the simulation of acute respiratory distress syndrome

Алимкина

Petrenko

2021

The work is devoted to the study of changes in the cellular composition of bronchoalveolar lavage over time in the modeling of acute respiratory distress syndrome (ARDS) in mice. ARDS was modeled by administering α-galactosylceramide and a mixture of lipopolysaccharide with a complete Freud’s adjuvant. After euthanasia, bronchoalveolar lavage was taken for analysis. On this basis, changes in the total number of white blood cells, the percentage of neutrophils and macrophages were assessed. It was found that the percentage of neutrophils in the ARDS group shows a statistically significant difference from that in the intact group, starting from 3 hours after modeling ARDS. Further, a statistically significant decrease in macrophages was observed.