Drug–drug interactions affected by the transporter protein, P-glycoprotein (ABCB1, MDR1): I. Preclinical aspects

When certain coadministered drugs interfere with the transport of one another at the P-glycoprotein (Pgp) level, we observe the phenomenon of “drug–drug interactions”. We describe here the physical and biochemical ways that drugs react with Pgp, the induction of Pgp by xenobiotics and the polymorphisms of Pgp related to drug–drug interactions. We also describe methods that can be used to detect potential drug–drug interactions. Among the widely used methods are flow cytometry, cell culture with polarized expression of Pgp, liposome and inside-out membrane preparations, ex vivo studies, in silico calculations, cDNA microarrays, in vivo mouse models, positron emission tomography (PET), and nuclear magnetic resonance (NMR) methods with live animals.