KINETIC OF ABSORPTION OF MIGU-6 AS A POTENTIAL PHARMACOTHERAPY OF ENDOTOXEMIA

• Published in: Vіsnik Naukovih Doslіdžen no. 1
• Main Authors: V. Lukianchuk, N. Meleschenko, I. Seyfullina, O. Shevchuk
• Format: Journal Article
• Language: Ukrainian
• Published: Ukrmedknyha Publishing House 01-04-2017
• Subjects: абсорбція; ендотоксемія; координаційні сполуки германію
• ISSN: 1681-276X; 2415-8798
• DOI: 10.11603/2415-8798.2017.1.7100

An actual problem of modern medicine is a treatment of endogenous intoxication syndrome. It is polyetiological emergency condition, which requires pathogenically substantiated rational pharmacotherapy. It was proven earlier that the original coordination compound of germanium, magnesium and oxyetylidendiphosphonic acid (MIGU-6) is safe and has a high detoxifying activity at endogenous intoxication (as crush syndrome also). The aim of the study – comparative pharmacokinetic characteristics of the absorption process of MIGU-6 in intact rats and in rats with posttraumatic endotoxemia. Materials and Methods. Experimental model is a pathological process that occurs in rats as a result of crushing of soft tissues of lower extremities. Original compound was administered as 1% solution at a dose of 140.6 mg/kg before the crushing. The pharmacokinetic of MIGU-6 was studied by determining the concentration of germanium in tissues of animals with crush syndrome and in intact animals. Samples to study were taken in 30 minutes, 1, 4, 8, 12 and 24 hours after administration of MIGU-6.  Comparative analysis of the following parameters was performed: absorption rate constant (K01), half-absorption period (t1/2,a), maximum serum concentration (Cmax), time to reach maximum serum concentration (tmax). Results of the studies and their discussion. Comparative analysis allows concluding that the process of absorption MIGU-6 in intact rats and in rats with posttraumatic endotoxemia goes fast enough. It was fixed higher concentrations of MIGU-6 in animals with crush syndrome, compared to healthy animals. Rate of absorption into the systemic blood flow was 0,71 h-1in healthy animals. In animals with crush syndrome it was 5.4–fold higher than those in healthy animals. Half-absorption period correlates with the absorption rate constant. Maximum serum concentration of MIGU-6 was significantly increased (152.85 μg/l) in case of endotoxemia compared to healthy rats (119.36 μg/l). tmax is 2.3-fold faster in group of animals with crush syndrome. Conclusions. Thus, in case of posttraumatic endotoxemia, pharmacokinetic parameters of MIGU-6 absorption, undergo significant changes, such as intensification of absorption of the compounds into the systemic blood circulation.