Russian MedicineRussian Medicine0869-21062412-9100Eco-Vector3835810.18821/0869-2106-2016-22-4-203-206Research ArticleThe effectiveness and safety of pharmacotherapy against the background of application of GliquidoneTitovDmitriy S.post-graduate student of chair of pharmacology with course of pharmacyi3762@yandex.ruPravkinS. K-The academician I.P. Pavlov Ryazanskiy state medical university1508201622420320621072020Copyright © 2016, Eco-Vector2016The study was carried out to investigate using rabbits in vivo effect of Gliquidone on functional activity of protein-carrier of glycoprotein-P (P-gp, ABCB1-protein). The activity of P-gp was evaluated according pharmacokinetics of its marker substrate - Fexofenadine after single endogastric introduction. The application of Gliquidone in dosage of 10 mg per 1 kg of body mass during 14 days resulted in no alteration of concentration of Fexofenadine, period of its partial ejection, area under pharmacokinetic curve “concentration-time” from zero to last point of blood sampling, area under pharmacokinetic curve “concentration-time” from zero to infinity and also time of holding of marker substrate, total clearance and absorption coefficient. All this testifies absence of effect of Gliquidone on functional activity of protein-carrier at the level of integral organism. No alterations of pharmacokinetic parameters of Fexofenadine at the 5th day of cessation of Gliquidone were observed.Gliquidoneglycoprotein-PABCB1-proteinгликвидонгликопротеин-РABCB1-белок[Якушева Е.Н., Черных И.В., Бирюкова А.С. Характеристика гликопротеина-Р как белка-транспортера лекарственных веществ. Российский медико-биологический вестник им. академика И.П. Павлова. 2011; (3): 142-8.][Якушева Е.Н., Черных И.В., Щулькин А.В., Котлярова А.А., Никифоров А.А. Половые различия функциональной активности и экспрессии гликопротеина-Р у кроликов. Российский физиологический журнал им. И.М. Сеченова. 2014; 100(8): 944-52.][Якушева Е.Н., Щулькин А.В., Черных И.В. Оценка принадлежности мексидола к субстратам, ингибиторам или индукторам гликопротеина-Р. Экспериментальная и клиническая фармакология. 2015; (3): 79-83.][Дедов И.И., Мельниченко Г.А., ред. Алгоритм специализированной медицинской помощи больным сахарным диабетом. 6-й выпуск. М.; 2013.][Якушева Е.Н., Бирюкова А.С., Щулькин А.В., Никифорова Л.В. Влияние тироксина на функциональную активность гликопротеина-Р в эксперименте. Российский медико-биологический вестник им. академика И.П. Павлова. 2011; (4): 49-53.][Якушева Е.Н., Черных И.В. Влияние экспериментальной подострой гипобарической гипоксической гипоксии на функциональную активность гликопротеина-Р. Российский медико-биологический вестник им. академика И.П. Павлова. 2013; (1): 60-4.][Якушева Е.Н., Щулькин А.В., Бирюкова А.С. Дозозависимое влияние тироксина на функциональную активность гликопротеина-Р в эксперименте. Биомедицина. 2012; (2): 53-60.][Ayrton A., Morgan P. Role of transport proteins in drug discovery and development: a pharmaceutical perspective. Xenobiotica. 2008; 38(7-8): 676-708.][Zhou S.F. Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica. 2008; 38(7-8): 802-32.][Hemauer S.J., Patrikeeva S.L., Nanovskaya T.N., Hankins G.D., Ahmed M.S. Role of human placental apical membrane transporters in the efflux of glyburide, rosiglitazone, and metformin. Am. J. Obstet. Gynecol. 2010; 202(4): 383.e1-7.][Choi Y.H., Lee D.C., Lee I., Lee M.G. Changes in metformin pharmacokinetics after intravenous and oral administration to rats withshort-term and long-term diabetes induced by streptozotocin. J. Pharm. Sci. 2008; 97(12): 5363-75.][De Gasparo M., Hostetter G., Desaulles P.A. Effect of gliquidone on insulin binding to rabbit erythrocytes. J. Endocrinol. 1983; 97(1): 97-103.][Guideline on the investigation of bioequivalence. European Medicines Agency. London; 2010.][Guidance for Industry Drug Interaction Studies - Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER); 2012.][Shen J., Hughes C., Chao C., Cai J., Bartels C., Gessner T. et al. Coinduction of glucose-regulated proteins and doxorubicin resistance in Chinese hamster cells. Proc. Natl. Acad. Sci. U S A. 1987; 84(10): 3278-782.][Liu H., Liu X., Jia L., Liu Y., Yang H., Wang G. et al. Insulin therapy restores impaired function and expression of P-glycoprotein in blood-brain barrier of experimental diabetes. Biochem. Pharmacol. 2008; 75(8): 1649-58.]