Keywords
Abstract
The problem of pharmacological protection of the body from complications of acute hypoxia, which develops in a confined unventilated space, confined space hypoxia (CSH), is relevant and requires immediate solution. Today, in terms of finding new drugs with high antihypoxic potential, the most promising are heterometallic complexes of germanium and 3d-metals (zinc, copper, manganese) with citric and tartaric acids. Toxicometric and screening studies proved high antihypoxic activity and harmlessness of the germanium – manganese (II) tartrate germanate (IV) coordination compound under the laboratory code OKAGERM-4.
The aim of the study – to carry out comparative pharmacokinetic analysis of OKAGERM-4 at the stage of its elimination from the central chamber under normal conditions and in the modeled CSH.
The experiments were performed on 48 nonlinear white rats of both sexes weighing 170–200 g, divided into two groups: control and experimental (rats in which CSH was modeled by placing them for 25 min in hermetic 10 cm3 sealed containers). In order to determine the pharmacokinetic profile, the level of OKAGERM-4 was determined by germanium content using the colorimetric method in blood serum 45 min, 3 h, 6 h and 24 h after a single intraperitoneal injection to rats at a dose of 96.8 mg/kg.
Based on the semi-logarithmic curves obtained, a number of pharmacokinetic parameters were directly calculated, those that characterize the processes of OKAGERM-4 elimination from the central chamber: t1/2β (norm) 0.26 h ± 0.05 h; t1/2β (CSH) 0.23 h ± 0.03 h; K10 (norm) 11.33 h–1 ± 4.90 h–1; K10 (CSH) 11.83 h–1 ± 3.16 h–1; MRT (norm) 1.37 h ± 0.28 h; MRT (CSH) 1.42 h ± 0.18 h; Clt (normal) 7.30 mL/h/kg ± 0.89 mL/h/kg; Clt (CSH) 7.36 mL/h/kg ± 0.55 mL/h/kg.
Thus, it has been experimentally established that the process of OKAGERM-4 elimination from the central chamber occurs approximately the same way regardless of the presence of hypoxic damage to the body.