5 research outputs found

    PHARMACOKINETIC RESEARCH OF POTENTIAL HYGOGLICEMIC DRUGS С7070

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    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

    Comparative study of the pharmacological effects of Venarus Plus, Venarus, and Detralex on L-NAME-induced endothelial dysfunction, venous tone and platelet aggregation

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    In the present study we compared the pharmacological activity of Venarus Plus, Venarus and Detralex 1000 mg on the reversion of endothelial dysfunction (ED), and on the effect on venous tone, vascular permeability, and platelet aggregation. We used 150 Wistar male rats, weighing 180-220 g, and 80 adult albino rabbits weighing 2800 - 3200 g. Endothelial dysfunction (ED) was induced with the non-selective inhibitor of NO synthase, N-nitro-L-arginine-methyl ether (L-NAME). Functional vascular tests and biochemical markers were used to determine the reversion of the functional disorders. The anti-inflammatory effects of the drugs was evaluated in rabbits using o-xylene. The venotonic effects of the compounds was carried out on an isolated segment of the rat portal vein with Ca2+ solutions at a concentration of 0.08-1.75 mM. Our results show that the maximum daily therapeutic dose of Venarus Plus, produces a significant decrease in the ED coefficient (СED), an increase in NO synthesis, and an extended ADP-induced platelet aggregation time. The studied drugs dose-dependently reduce vascular permeability disorders caused by the application of o-xylene, which was manifested in a profound decrease the size of spots and the extension of the time interval before their onset. To study the Ca2+-mediated smooth muscle response, showed that the maximum force of vein contraction occurs with a higher dosage of drugs in the presence of a lower concentration of Ca2+, the effects of the drugs are comparable
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