CNS drug-drug interactions mediated by p-glycoprotein

Drug-resistance is one of major obstacles of CNS disorders in clinical settings. The efflux pump, P-glycoprotein, can be induced through chronic treatment leading to non-responsive patients. It is critical to figure out the underlying drug-drug interactions (DDIs) in order to reasonably modulate P-gp expression and function. In this study, I summarized in vitro and in vivo study of CNS drug-drug interactions as well as potential associations between P-gp and pharmaco-resistant CNS disorders. Aiming to establish a methodology in studying CNS DDIs, different model correlations, interplay of metabolism and transport, collaboration of efflux transporters, P-gp expression and function etc. should be considered. In addition, P-gp serves as an important target in drug development. P-gp inhibitors, inducers and even non P-gp substrates are important lead compounds in treating refractory CNS disorders mediated by P-gp.