BACKGROUND: Biliary excretion is a major elimination route of many drugs and 
their metabolites. Hepatobiliary elimination is a vectorial process involving 
uptake transporters in the basolateral hepatocyte membrane, possibly Phase I and 
Phase II metabolizing enzymes, and ATP-dependent efflux pumps in the apical 
hepatocyte membrane.
OBJECTIVES: Because many drugs and their metabolites are anions, this review 
focuses on transporters involved in their hepatocellular uptake (members of the 
organic anion transporting polypeptide (OATP) family) and biliary elimination 
(apical conjugate efflux pump ABCC2/MRP2).
METHODS: The molecular and functional characteristics of the human OATP and 
ABCC/MRP transporters are presented, including a detailed overview of endogenous 
and drug substrates. Examples illustrate the interplay of transporters with 
Phase II conjugating enzymes. Model systems to study the vectorial transport of 
organic anions are also discussed.
RESULTS/CONCLUSIONS: OATP uptake transporters, conjugating enzymes, and 
ABCC2/MRP2 work in concert to enable the hepatobiliary elimination of anionic 
drugs and their metabolites. It is increasingly important to understand how 
genetic variants of these transporters and enzymes influence the interindividual 
variability of drug elimination.