P-glycoprotein: a defense mechanism limiting oral bioavailability and CNS accumulation of drugs.

摘要: Transport by ATP-dependent efflux pumps such as P-glycoprotein is an increasingly recognized determinant of drug disposition. does not only contribute to multidrug resistance (MDR) in tumor cells, it also expressed normal tissues with excretory function liver, kidney and intestine. Apical expression results reduced absorption from the gastrointestinal tract enhanced elimination into bile urine. Moreover, endothelial cells blood-brain barrier prevents entry certain drugs central nervous system. Human has been shown transport a wide range structurally unrelated digoxin, quinidine, cyclosporine HIV-1 protease inhibitors. Drug administration knock-out control mice provided data on importance for after oral penetration through barrier. were used identify inhibition P-glycoprotein-mediated mechanism interactions digoxin-quinidine interaction. Studies humans indicate particular intestinal bioavailability immunosuppressant cyclosporine. induction rifampin now identified major underlying digoxin plasma concentrations during concomitant therapy. In summary, functions defense mechanism, which determines CNS drugs. Modification important humans. However, disposition its metabolites frequently determined P-glycoprotein, but drug-metabolizing enzymes possibly transporters other than [e.g. members MRP family (MRP = resistance-associated proteins)].