DRUG TRANSPORT IN THE LIVER - Drug Transporters: Molecular Characterization and Role in Drug Disposition - page 389

of the hepatocyte (e.g., intracellular trafficking proteins, proteins on the endoplasmic
reticulum) and their role in hepatobiliary drug/metabolite disposition, efficacy, and
toxicity await exploration. Continued characterization, validation, and refinement of
existing model systems are needed. A road map for use with existing models would
be particularly helpful in the drug development process to delineate what model(s)
should be used to answer which questions, and in what order, and to address how
data should be interpreted and used most effectively in drug development. In addition,
the development of new techniques, tools, and/or model systems that address spe-
cific concerns with existing approaches (e.g., species-dependent differences, sample
throughput, physiologic relevance), and that can be used to answer both mechanistic
and applied questions regarding hepatobiliary transport, is needed. Such tools will be
useful in enhancing our understanding of how drugs and metabolites move through
the human hepatocyte to sites of action, biotransformation, and/or excretion. This
knowledge is fundamental to the optimization of drug therapy to achieve desirable
therapeutic outcomes and to minimize the incidence of side effects, including drug-
induced hepatotoxicity.
Acknowledgments
This work was supported in part by the National Institutes of Health grant R0I
GM41935.
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