6

DRUG TRANSPORTERS IN DRUG

DISPOSITION, DRUG INTERACTIONS,

AND DRUG RESISTANCE

CINDYQ. XIA,JOHNNYJ. YANG,ANDSURESHK. BALANI

6.1 INTRODUCTION

Evolution has created ways for living beings to adapt to changes in nature, and
to defend themselves against threats to their existence. Only in the past century
have we started to grasp the complex nature of the biology and biochemical
processes occurring in human beings. Transporter proteins are involved in
some of these processes. Essentially, the body cannot function well without the
transporters that allow uptake of, for example, nutrients and efflux of harmful
substances, like cytotoxins, from cells. The role of transporters was realized
well over three decades ago (Juliano and Ling, 1976), much after the emergence
of knowledge on CYPs. We are currently following in the footsteps of CYPs
knowledge-based development, and steadily increasing our understanding of
transporter functions, types, locations, and their roles in a qualitative fashion.
Only in the past decade have we found that some CYPs work in concert with
transporters. It is just a matter of time till we have means of quantitative
assessment of the role of transporters in drug disposition and interactions in
whole bodies. It is a welcome change to see, for the first time, considerations
for transporters-based drug–drug interactions (DDI) appearing in the FDA’s
‘‘draft guidance on DDI studies’’ in September 2006 (www.fda.gov/cder/
guidelines.htm). This should stimulate further standardization of processes and
eventually harmonization of ways and when to conduct DDI studies.

Drug Metabolism in Drug Design and Development, Edited by Donglu Zhang, Mingshe Zhu
and W. Griffith Humphreys
Copyright#2008 John Wiley & Sons, Inc.

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