chapter  12
22 Pages

Transporter-Mediated Drug Interactions: Molecular Mechanisms and Clinical Implications

Most mammalian cell membranes contain various transporter systems, which are effective in taking up a great number of endogenous and exogenous molecules that the cells need, or in extruding endogenous and exogenous molecules that the cells want to get rid of. In humans, some of these transporters also play a significant role in the processes of drug absorption, distribution, metabolism, and excretion (ADME) of drugs. With the great advance in molecular biology and biotechnology, many drug transporters have been identified and characterized over the last 10 years. Although the importance of the role of drug transporters in the processes of ADME is becoming well recognized, our understanding of their physiological function is still nascent. In spite of a large body of information on the kinetic characterization of transporters in cell culture models and heterologous expression systems, there are still large gaps in our knowledge about how to utilize the information obtained from in vitro studies to interpret the in vivo kinetic behavior of drugs and for developing new drug candidates that are absorbed, distributed, or excreted by means of transporters (1,2).