Zhukova N. Experimental pharmacokinetics of 3-alkoxy-1.4-benzodiazepine-2-one (ethoxozepam)

The dissertation is dedicated to studying of absorption, distribution, metabolism and elimination processes of 14C-ethoxozepam. Via condensation of the corresponding 3-chloroderivative 1.4-benzodiazepine with 14C-ethanol the 14C-labeled sample with specific activity 0.7GBk/mol and radiochromaographic purity 96.2 % had been obtained. It was found that after intravenous administration substance partially (up to 14 % of the dose administered) secreted to the gastro-intestinal tract, while fully and readily being absorbed after intragastral administration. Ethoxozepam's concentration in blood, brain and liver is described with the one-compartment pharmacokinetic model. In the organism the studied substance undergoes metabolism - after intravenous administration in organs and tissues the unchanged substance quantity is from 50 to 70 % of the total radioactivity. In vitro the radioisotope label elimination from structure (37,1 11,7% of the total maximum biotransformation of lipophilic metabolites) had been found and the scheme of it's possible transformation had been suggested. After intravenous administration the total quantity of radioactivity excreted is 18,0 ± 3,5 %, while after intragastral - 29,0 ± 8,0 % of the dose administered that proves the impact of the intense biotransformation and izitope elimination from ethoxozepam molecule in vivo.