Human P-glycoprotein differentially affects antidepressant drug transport: Relevance to blood-brain barrier permeability

Abstract The pharmacological concept that inhibition of the drug efflux pump P-glycoprotein (P-gp) enhances brain distribution of the antidepressant imipramine in the rat has recently been demonstrated. To determine if these findings are relevant to humans, the present study investigated if imipramine is a transported substrate of human P-gp. Furthermore, additional experiments were carried out to determine if findings in relation to imipramine and human P-gp would apply to other antidepressants from a range of different classes. To this end, bidirectional transport experiments were carried out in the ABCB1-transfected MDCKII-MDR1 cell line. Transported substrates of human P-gp are subjected to net efflux in this system, exhibiting a transport ratio (TR) â