By Patrick T. Ronaldson and Steven W. Louie
Transporters are critical determinants of drug disposition and drug efficacy. Research has identified and characterized multiple putative uptake and efflux transporters. For example, the ATP-dependent efflux transporter P-glycoprotein has been extensively studied in several normal and pathological cell types and is well known to be a critical determinant of tissue penetration for drugs. Other efflux transporter systems such as multidrug resistance proteins (Mrps) and breast cancer resistance protein (Bcrp) have been the subject of an intense research focus over the past decade. More recently, considerable interest has centered on uptake transporters, particularly with respect to their utility in drug delivery to specific organs and tissues. Indeed, the net contribution of influx and efflux transporters is a critical determinant of all aspects of pharmacokinetics.
However, transport systems are not static in nature, a pharmacological fact that renders the study of drug transporters highly complex. Advances in molecular pharmacology have shown that transport systems are extremely dynamic and can be modulated by disease and by drugs themselves. Furthermore, age, sex, and genetic differences in transporters can contribute to vastly different pharmacokinetic and/or pharmacodynamic profiles within human populations. This implies that an understanding of membrane transport mechanisms is required for development of precision medicine strategies to treat a multitude of diseases. In addition to their involvement in drug disposition, transporters can also contribute to clinically significant drug-drug interactions. The role of transporters in drug-drug interactions implies a need to understand mechanisms of membrane transport to avoid drug-related toxicity and to improve drug safety.
Concepts in transporter pharmacology are new to many pharmaceutical scientists, suggesting a significant training gap. An exceptional opportunity to fill such gaps in knowledge is to participate in the variety of cutting-edge education being provided on the subject this year. This includes attending the 2016 AAPS/International Transporter Consortium (ITC) Joint Workshop on Drug Transporters in ADME: From the Bench to the Bedside. This workshop builds from multiple highly successful AAPS workshops on drug transporters that have been held over the past decade. World-renowned thought leaders will discuss state-of-the-art transporter science. The meeting will also provide a forum for trainees and principal investigators to present their work in poster sessions. There are multiple opportunities for networking during the meeting as well as a mentoring luncheon where graduate students and postdoctoral fellows can meet and receive career advice from established transporter scientists. Such networking will facilitate the next generation of transporter studies to move from the bench to the bedside leading to development of better drugs and more effective therapies.
To get you warmed up for this event, AAPS will be offering two open-access and free webinars on transporter topics. Join the discussion on Predicting Transporter-Mediated Hepatic Disposition and Drug-Drug Interactions on February 25 and then again to explore Transporter Biomarkers on April 14. Register today to join the discussion!
On behalf of the AAPS Drug Transport focus group, we invite you and your colleagues to collaborate with us on transporters this coming year. You will not be disappointed!