Chapter 1:Membrane Transporters: Fundamentals, Function and Their Role in ADME

The concept that membrane transport proteins could facilitate the flux of molecules across eukaryotic cell membranes was still in its infancy in the middle of the 20th century. Today, as our knowledge of this area of science has expanded, it is now recognized that they play an important role in the absorption, distribution, metabolism and elimination (ADME) of drugs, as well as being involved in the movement of endogenous compounds within and between cells. This chapter explores the role of transporters in drug ADME, describing their different mechanisms of action, their location within the body, how different factors can affect transporter form and function, as well as giving a concise overview of some of the key aspects to consider in the development of new drug entities. It is intended to give a broad outline of the fundamental concepts, with topics ranging from an introduction to current nomenclature and the differing expression levels in animals and humans through to an explanation of the drug development process and transporter investigations within the pharmaceutical industry. Relevant examples are given throughout the text, with links to reviews and current transporter databases included for those wishing to pursue the area further. As the primary focus is on transporters currently known to be clinically relevant, the transport of oligonucleotides and proteins is not covered within this overview.