350 rub
Journal №9 for 2014 г.
Article in number:
Use of the capillary electrophoresis for studying of pharmacokinetics of new SYK-kinazy inhibitor
Authors:
S.P. Senchenko - Ph.D. (Pharm.), Associate Professor, Department of Pharmaceutical and Toxicological Chemistry, Pyatigorsk Medico-Pharmaceutical Institute-Branch to Volgograd State Medical University. E-mail: asp_nauka@mail.ru
H.G. Chilov - Ph.D. (Chem.), Senior Research Scientist, N.D. Zelinsky of Institute of Organic Chemistry, Russian Academy of Sciences, General Director of LLS «Molekulyarnye Tekhnologii» (Moscow)
F.N. Novikov - Ph.D. (Chem.), Research Scientist, N.D. Zelinsky of Institute of Organic Chemistry, Russian Academy of Sciences (Moscow)
A.Y. Terekhov - Ph.D. (Pharm.), Associate Professor, Department of Morphology and Pathology, Pyatigorsk Medico-Pharmaceutical Institute-Branch to Volgograd State Medical University
H.G. Chilov - Ph.D. (Chem.), Senior Research Scientist, N.D. Zelinsky of Institute of Organic Chemistry, Russian Academy of Sciences, General Director of LLS «Molekulyarnye Tekhnologii» (Moscow)
F.N. Novikov - Ph.D. (Chem.), Research Scientist, N.D. Zelinsky of Institute of Organic Chemistry, Russian Academy of Sciences (Moscow)
A.Y. Terekhov - Ph.D. (Pharm.), Associate Professor, Department of Morphology and Pathology, Pyatigorsk Medico-Pharmaceutical Institute-Branch to Volgograd State Medical University
Abstract:
Rheumatoid arthritis is characterized by activation of several various types of immune cages. Kinases (group of the enzymes belonging to the class of transferases) play the leading role in activation of the aberrantny immune answer and, therefore, can be a target for treatment of autoimmune and oncological diseases. Among protein kinase at RA it is actively studied spleen tyrosine kinase (Syk), thus clinical tests showed reliable efficiency in treatment of RA of inhibitors of this type of kinases. It is important to note that research of new medicines is impossible without use of reliable methods of the analysis necessary at studying of their pharmacokinetics and bioavailability. In this regard the purpose of this work was studying of pharmacokinetics of new Syk-kinases inhibitor (the code of MT-Syk-03 representing derivative diamino triazine) in serum of blood of mice with use of a capillary electrophoresis.
Studied substance entered intragastrically an animal in a dose of 200 mg/kg of body weight. Substance extraction from serum carried out by means of chloroform which further drove away. After the chloroform distillation by the rest added 100 мкл leading electrolyte and 400 мкл waters, well suspended, mixed and centrifuged 10 min. at 7000 min-1. For definition of free substance in serum of blood the method of a capillary electrophoresis was used. Conditions of the analysis were the following: thermostatically controlled quartz capillary with a working length of 65 cm and with a diameter of 75 microns. temperature of experience made 20 0C and voltage of +25 kV. Experiment made in the conditions of a micellar electrokinetic chromatography, thus as leading electrolyte used sodium tetraborat decahydrat solution with concentration of 2 mg/ml and additives of sodium dodecylsulfate (concentration of 10 mg/ml) and urea (concentration of 400 mg/ml). Input of test was carried out hydrodynamic by 150 Mbar-s. Detecting carried out spectrophotometric at 220 nm. For an assessment of pharmacokinetics counted constants of speeds of absorption, elimination, the maximum concentration of a preparation in blood and time of its achievement, the semi-absorption and semi-removal periods, average time of keeping and some other. From the received results follows that absorption at animals of substance of MT-SYK-03 happens rather slowly, considering the high speed of a metabolism at mice. Process of distribution and metabolism can be considered within single-chamber model with absorption. Thus the constant of speed of elimination is 3,4 times less than a constant of speed of absorption. This fact can say about long circulation of this substance in an organism that in turn can testify to its linkng with proteins of blood.
Pages: 4-7
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