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.
Aszalos
Adorjan
A
Laboratory of Cell Biology, 37 Convent Drive, Room 2108, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. aszalosa@mail.nih.gov
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D004347:Drug Interactions; D005434:Flow Cytometry; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D049268:Positron-Emission Tomography
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008081:Liposomes