FUNCTIONAL ACTIVITY OF P-GLYCOPROTEIN WITH UNDERLYING BRAIN ISCHEMIA

Background. P-glycoprotein (Pgp) is an efflux ATP-dependent membrane transporter protein that removes a wide range of lipophilic endo- and xenobiotics, including drugs, from the cells into the extracellular space. Its activity can change under the influence of some factors and substances. Aim. The aim of the experiment was to study functional activity of Pgp at an organism level after the permanent common carotid artery occlusion. Materials and Methods. The study was performed on 14 mature male chinchilla rabbits (3500-4300 g). The animals were divided into 2 groups: in the 1st group Pgp functional activity was stu-died after a ‘false' operation (n=5); in the 2nd group the transporter activity was studied with the underlying unilateral common carotid artery occlusion (n=9). Pgp functional activity was evaluated by pharmacokinetics of the marker substrate of the transporter – fexofenadine – after its single oral administration at the dose of 67.5 mg/kg b. w 5 days before and 7 days after the surgery. Results. Before the experiment pharmacokinetic parameters of fexofenadine in rabbits of the 1st and the 2nd groups did not show any statistically significant differences (p>0.05). Both ‘false' operation and occlusion of the common carotid artery did not produce a reliable effect on the pharmacokinetics of Pgp marker substrate: it did not change in comparison with the initial profile. Besides, no significant differences were revealed between the 1st and 2nd groups on the 7th day of the study after ‘false' operation and common carotid artery occlusion, respectively. Conclusions. Unilateral common carotid artery occlusion did not lead to a change in the functional activity of Pgp at the level of the whole organism, as determined by the pharmacokinetics of its marker substrate − fexofenadine.