V.G. Belikov, B.V. Borovskii, N.S. Lyakhova

The staff of the Department of organic chemistry of the Russian state pedagogical University of a name And. Herzen (d.Saint-Petersburg) was synthesized a new derivative of γ-aminobutyric acid: 4-amino-3-(pyridyl-3)-butane acid dihydrochloride (RGPU-195). Research carried out by pharmacologists, Volgograd state medical University, has demonstrated a high pharmacological activity of this compound. An important stage of pharmacological tests are pharmacokinetic studies to examine the patterns of behavior of medicinal substances in an organism. The aim of the research development of a technique of isolating RGPU-195 of blood plasma and a study of the pharmacokinetic characteristics of RGPU-195. MATERIALS AND METHODS. For the quantitative determination of RGPU-195 we have developed a method of capillary electrophoresis. This method allows to avoid the influence of the background and is the most selective. The tests were carried out using the system Drops 105 (St. Petersburg). When selecting the optimal conditions of extraction of RGPU-195 of the blood plasma was studied the simultaneous influence on the degree of extraction of the nature of the organic solvent, pH buffer solution, the presence of electrolytes. The results of the experiment the highest total output of RGPU-195 was obtained when using the ethylacetate, adding electrolytes increased the degree of extraction of RGPU-195 of blood plasma. The experiments on the study of the pharmacokinetics of derivative GABA - RGPU-195 were carried out in 54 white rats line Wistar mass of 280-300 g with observance of all rules and the International recommendations of the European Convention for the protection of vertebrate animals used for experimental studies (1997). The substance of RGPU-195 was administered orally to rats in the effective therapeutic dose of 50 mg/kg. The quantity of the substance was determined in the blood plasma. Samples of blood, the oral route of administration is made through 0,5; 1; 2; 3; 4; 6; 8; 12 hours after introduction of the preparation. Control served as the blood of the intact animals. A number of standard pharmacokinetic parameters recommended for the evaluation of the pharmacokinetics. RESULTS AND THEIR DISCUSSION. In the study, was defined pharmacokinetic profile RGPU-195 in the blood plasma after oral administration, the rats which has a phase of increasing concentration or phase of absorption, for which there is a maximum concentration in the blood plasma. The second part of the time curve (descending), characterizes the elimination of the substances from the blood plasma (phase reduce the concentration of the substance). The analysis of time suction subject of the research shows that after 30 minutes from the start of the introduction of the blood contains of 1.85 g/kg, the maximum concentration of 6.8 g/ml) is found in the blood to the third hour of the study. The substance almost completely withdrawn from the blood to the 8 hour experiment, and traces of explosives are in the blood within 12 hours after the injection. Analysis of pharmacokinetic parameters testifies to the fact that the half-life period of RGPU-195 is 3,2 hours. The results of study of the pharmacokinetics of RGPU-195 in experiments on animals will help in further study in clinical trials with the purpose of creation of the medicinal product. CONCLUSIONS. Developed a method of isolating RGPU-195 from the blood plasma of animals, studied the pharmacokinetic parameters of the substance. Maximum concentration of the substance in the blood plasma after oral administration, the rats were observed at the third hour of the experiment, the traces are found in the blood plasma of animals through 12 hours after the injection.