title: Principles and experimental considerations for in vitro transporter interaction assays.
abstract: Drug transporters are now universally acknowledged as important determinants of the absorption, distribution, metabolism and excretion of both endogenous and exogenous compounds. Altered transporter function, whether due to genetic polymorphism, DDIs, disease, or environmental factors such as dietary constituents, can result in changes in drug efficacy and/or toxicity due to changes in circulating or tissue levels of either drugs or endogenous substrates.Prediction of whether and to what extent the biological fate of a drug is influenced by drug transporters, therefore, requires in vitro test systems that can accurately predict the risk and magnitude of clinical DDIs. While these in vitro assessments appear simple in theory, practitioners recognize that there are multiple factors that can influence experimental outcomes. A better understanding of these variables, including test compound characteristics, test systems, assay formats, and experimental design will enable clear, actionable steps and translatable outcomes that may avoid unnecessary downstream clinical engagement. This chapter will delineate the role of these variables in improving in vitro assay outcomes.
authors: Absorption Systems LP, 436 Creamery Way, Suite 600, Exton, PA, USA.
authors: Sid
authors: S
authors: Bhoopathy
authors: Chris
authors: C
authors: Bode
authors: Vatsala
authors: V
authors: Naageshwaran
authors: Erica A
authors: EA
authors: Weiskircher-Hildebrandt
authors: Ismael J
authors: IJ
authors: Hidalgo
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000379:methods*; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism
chemical_list: D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations