A Method of Analysis of the Functional Activity of P-Glycoprotein in the Blood–Brain Barrier

This article describes a method for testing the functional activity of the transporter protein P-glycoprotein (Pgp) in the blood–brain barrier in Wistar rats. This method is based on the study of the pharmacokinetics of fexofenadine, a marker substrate of Pgp, after its single intravenous administration at a dose of 10 mg/kg. Quantitative determination of fexofenadine in rat blood plasma and homogenate of the rat cerebral cortex was performed by high performance liquid chromatography with ultraviolet detection. To assess the permeability of the blood–brain barrier and Pgp activity, we proposed to calculate the area under the fexofenadine concentration in the cerebral cortex–time curve (AuC 0−t(brain) ), which reflects the total amount of fexofenadine in the brain. The adequacy of the developed method was confirmed when fexofenadine was administered to rats in the presence of an inducer and an inhibitor of the transporter protein.