INFLUENCE OF HYDROLYZATE OF POLYSACCHARIDE COMPLEX OF TANSY (TANACETUM VULGARE) FLOWERS ON ABCB1-PROTEIN ACTIVITY IN VIVO

Background. ABCB1-protein is a membrane glycoprotein with ATP-ase activity directed at the efflux of a wide range of endogenous and exogenous substances. Pharmacological inhibition of functional activity or of synthesis of this transporter is a perspective aim to increase the effectiveness of pharmacotherapy of many diseases. Aim. To study the effect of hydrolyzate of polysaccharide complex of tansy flowers on ABCB1 protein functional activity in vivo. Materials and Methods. Hydrolyzate of the polysaccharide complex was isolated from the air-dried tansy flowers (Phytopharm, Russia) using the original method, with subsequent acid hydrolysis to the average molecular weight 3800 Da. The transporter activity was assessed by the pharmacokinetics of its marker substrate – fexofenadine. For this, fexofenadine was intragastrically (67.5 mg/kg b.w.) administered to 6 animals, with subsequent taking blood in 11 time points for quantitative analysis of fexofenadine by HPLC method, and for calculation of its pharmacokinetic parameters. The activity of ABCB1-protein was estimated in intact rabbits (control), after a single intragastric introduction of hydrolyzate of polysaccharide complex to the same rabbit sat a dose of 50 mg/rabbit, and a single introduction of hydrolyzate of polysaccharide complex at a dose of 150 mg/rabbit. Results. It was found that after introduction of hydrolyzate of polysaccharide complex oftansy flowers (50 mg/animal) to rabbits, not a single of the estimated parameters of fexofenadine pharmacokinetics reliably differed from control levels (p>0.05). However, hydrolyzate of polysaccharide complex of tansy flowers introduced at a higher dose (150 mg/rabbit) led to reliable 3.2-fold increase in AUC0-t of fexofenadine (90% CI 1.69-6.05, p=0.014) in comparison with control. Conclusion. This dynamics of fexofenadine pharmacokinetic parameters showed that hydrolyzate of polysaccharide complex oftansy flowers at a dose of 150 mg/rabbit led to increase inthe intestinal absorption and in the plasma level of the marker substrate of ABCB1-protein, but did not influence the intensity of its excretion which evidences the direct in hibitory effect of hydrolyzate of polysaccharide complex of tansy flowers on the functional activity of ABCB1-protein in mucosa of the small intestine.