PHARMACOKINETIC RESEARCH OF POTENTIAL HYGOGLICEMIC DRUGS С7070

Introduction: The development of effective drugs for the treatment of diabetes is one of the urgent problems of modern medicine; we conducted pharmacokinetic studies of the innovative hypoglycemic drug - C7070, in rabbits and rats. Materials and Methods: The object of the study was substance C7070. Two methods of administration have been studied: intravenously and intragastrically. The concentration of C7070 is determined in blood plasma by a sensitive and selective HPLC method with tandem mass spectrometry detection. The range of detection was from 0.02 μg to 3876.00 μg in 1 ml of plasma in the animals under study. Chromatographic separation was performed on a 150 × 3.0 mm column of Zorbax Eclipce XDB C18 with a particle size of 3.0 μm (Agilent technologies, USA). To obtain stable results, a Zorbax Eclipce XDB C18 (Agilent technologies, USA) protection column of 12.5 × 3.0 mm with a particle size of 5.0 μm was used at 40 ° C for all analytical cycles. Ballast proteins in the test solutions were precipitated with acetonitrile followed by extraction of the analyte with ultrasound. Results and its Discussion: With intragastric administration, the maximum concentration (Cmax) of C7070 in blood plasma reached, on average, in rabbits through (tmax) 60 ± 0.1 minutes, in rats after 170.0 ± 79.8 minutes and was 34.6 ± 7.3 μg/ml and 17.6 ± 1.4 μg/ml, respectively. The half-life (t1/2) was prolonged and was 291.8 ± 17.1 minutes for rabbits and 225.2 ± 12.4 minutes for rats. The absolute bioavailability (fa) of C7070 in rabbits was 78.2 ± 1.0%, in rats 18.1 ± 2.0%. When administered intravenously, Cmax C7070 in blood plasma averaged 123.1 ± 23.7 μg/ml in rabbits and 337.6 ± 40.5 μg/ml in rats. The half-life period (t1/2) was prolonged and amounted to 225.5 ± 15.9 minutes for rabbits and 154.1 ± 5.1 minutes for rats. The Conclusion: The pharmacokinetic characteristics of a potential hypoglycemic drug C7070 in animals (rats, rabbits) under two routes of administration, intra-gastrointestinal and intravenous, were studied. The parameters obtained can be useful for clinical application and further studies of C7070 drugs based on it. Key words: C7070, diabetes mellitus, hypoglycemic agents, blood plasma of rabbits and rats, high-performance liquid chromatography, pharmacokinetics

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