Drug Transporters in Drug Efficacy and Toxicity

Abstract

Drug transporters are now widely acknowledged as important determinants governing drug absorption, excretion, and, in many cases, extent of drug entry into target organs. There is also a greater appreciation that altered drug transporter function, whether due to genetic polymorphisms, drug-drug interactions, or environmental factors such as dietary constituents, can result in unexpected toxicity. Such effects are in part due to the interplay between various uptake and efflux transporters with overlapping functional capabilities that can manifest as marked interindividual variability in drug disposition in vivo. Here we review transporters of the solute carrier (SLC) and ATP-binding cassette (ABC) superfamilies considered to be of major importance in drug therapy and outline how understanding the expression, function, and genetic variation in such drug transporters will result in better strategies for optimal drug design and tissue targeting as well as reduce the risk for drug-drug interactions and adverse drug responses.

The experience of Avicenna and possibility to improve the diabetes treatment

“…Он отмечал, что употребление кислых продуктов вызывает изменение «мизаджа» организ-ма человека в «холодную» (кислую, ацидную) диабе-тогенную сторону. Современной наукой доказано, что после приема повышенных доз кислых продук-тов, содержащих такие органические кислоты, как лимонная, яблочная, уксусная, аскорбиновая, щаве-левая, а также такие кислотные эквиваленты, как Cl -, PO4 -, SO4 -, наблюдается сдвиг рН в сторону ацидо-за [16][17][18][19]. Возникновение же ощелачивающего эф-фекта зависит от содержания в составе продуктов питания щелочных эквивалентов, таких как калий, натрий, магний и др.…”

Genetic Biomarkers in Epilepsy

“…While it was traditionally thought that drugs enter cells by passive diffusion it is now widely acknowledged that transporters (proteins integral to the plasma membrane facilitating the movement of compounds in and out of cells) are major determinants of drug absorption and elimination, as well as entry into the target organ (Fig. 2) [57][58][59][60]. The potential role of drug transporters in resistance to antiepileptic drug therapy is currently being intensely discussed [61].…”

Cell Surface Membrane Proteins as Personalized Biomarkers: Where we Stand and Where we are Headed

“…The latter mostly belong to the SLC22 group, which include both anionic (OATs) and cationic drug transporters (OCTs and OCTNs), and the SLCO (formerly SLC21) family (e.g., OATP1B1). A detailed discussion of the role of these transporters in drug application and development is provided in recent extensive reviews [27,28]. n Structural proteins Structural protein components of cellular mem branes include various cytoskeletal proteins, inte grins, numerous members of the immuno globulin superfamily and other proteins modulating cell-cell interactions.…”