The article describes modern approaches for testing of drugs belonging to substrates and inhibitors of P-glycoprotein (Pgp, ABCB1-protein, MDR1-protein) according to the recommendations of Food and Drug Administration (United States) and European Medicines Agency. In vitro methods on cell lines with hyperexpression of the transporter are presented. The same analysis was done on human colon adenocarcinoma cell line (Caco-2).

Inhibition of Pglycoprotein transporter protein (ABCB1protein, Pgp) is a promising method to increase the effectiveness of pharmacotherapy in different pathologies: neoplastic diseases, epilepsy, cerebral circulation disorders. Pgp is a large transmembrane protein that provides efflux of a wide range of endo and xenobiotics from cells, and plays a significant role in pharmacokinetics of many medical drugs. Nowadays not a single synthetic inhibitor of the transporter is used in clinical practice due to nonselectivity of action, toxicity and high cost. Medicinal herbal remedies possess different pharmacological and therapeutic effects, rarely cause side effects and are economically accessible. This review presents the results of experiments in which affiliation of the oligo and polysaccharides to substrates and inhibitors of Pgp was analyzed, and which precondition further studies of other plant derived polysaccharides. Possibilities of using plant derived nonstarch polysaccharides in complex therapy of tumors are described, since along with potential inhibition of the transporter, they possess an antitumor effect and can also assist in correction of side effects of cytostatics. The prospects of using plant derived nonstarch polysaccharides for improvement of the effectiveness of neuroprotective therapy are presented, because they not only can increase the penetration of neuroprotective drugs across the bloodbrain barrier through Pgp inhibition, but also possess their own neuroprotective activity, as well as a number of pharmacological effects that can give a positive result in the complex treatment of brain pathologies. Thus investigations of plant nonstarch polysaccharides, their isolation and development of medical drugs on their basis is a promising direction of modern medicine.

P-glycoprotein (Pgp, ABCB1-protein) is a membrane transporter protein that plays the key role in pharmacokinetics of drugs with a broad spectrum of action. Substrates of this transporter are some medical drugs (antibacterial, antiretroviral, hypotensive) that are prescribed to pregnant women for long-term intake, sometimes throughout the whole gestation period. Aim to study the activity of Pgp on the organism level in rabbits of Soviet Chinchilla breed in pregnancy. Materials and Methods. The study was performed on 21 Soviet Chinchilla female rabbits (3000-3500 g). The animals were divided into 3 series. The first series (n=6) included rabbits with 7 days of pregnancy; the second series (n=5) - animals with 14 days of pregnancy; the third series (n=10) - rabbits with 21 days of pregnancy. 7 Days before the study and in the indicated gestation periods, functional activity of Pgp was assessed by the pharmacokinetics of marker transporter substrate – fexofenadine, after its single oral introduction (67.5 mg/kg). Besides, serum concentrations of progesterone, estradiol, testosterone and prolactin were determined by radio immune method Results. In all the studied gestational periods, serum concentrations of estradiol, testosterone and prolactin did not significantly differ from those before pregnancy, but the level of progesterone in blood serum was significantly elevated above the norm. On the 7th day of pregnancy pharmacokinetic parameters of fexofenadine did not show any reliable changes as compared to the initial va-lues. On the 14th day of pregnancy a reliable increase in Cmax, AUC0-t, T1/2 of fexofenadine was noted as compared to the parameters before pregnancy, which indicates a decrease in Pgp functional activity on the organism level. On the 21st day of pregnancy Cmax of fexofenadine remained elevated. Other pharmacokinetic parameters of fexofenadine did not show reliable changes. Conclusion. Reduction in Pgp functional activity, determined by the pharmacokinetics of its marker substrate (fexofenadine), was noted in rabbits of Soviet Chinchilla breed on the 14th and 21st days of pregnancy with the underlying significant increase in progesterone level.