METHODS OF IDENTIFICATION OF DRUGS AS P-GLYCOPROTEIN SUBSTRATES

The article presents an original method for determining belonging of drugs to the substrates of the transport protein P-glycoprotein (Pgp). This methodics is based on a comparison of the pharmacokinetic parameters of the test substrate before and after a course of administration of the inductor (rifampicin) and inhibitor (verapamil) of the transport protein. If the content of test substance in organism is reduced after Pgp inductor administration, and increased after the inhibitor administration, we conclude that this substance is Pgp substrate. For approbation of developed technique we examined by blind method the pharmacokinetics of fexofenadine - known Pgp substrate at a dose of 67,5 mg/kg, before and after the 14-days administration of rifampicin (40 mg/kg twice daily) and verapamil (a daily dose of 20 mg/kg three times a day). It was revealed that after a course administration of verapamil maximum concentration of fexofenadine, its area under the concentration-time curve and half-life were significantly increased, as well as the time of maximum concentration was decreased. In contrast, rifampicin course administration resulted in a decrease in the area under the curve concentration-time and an increase in total clearance of marker substrate of Pgp, wich proves the adequacy of methods.

P-glycoprotein, fexofenadine, rifampicin, verapamil, pharmacokinetics, P-glycoprotein substrate, methods