Excretion of Drugs and Their Metabolites into the Bile

It is well documented that many approved drugs and/or their metabolites can be secreted into the small intestine through the bile and subsequently reabsorbed to form a circulation, which could significantly alter the drugs' pharmacokinetic profiles and efficacy. Thus, enterohepatic circulation driven by biliary secretion is required by the FDA to be included in the drug labels. Several factors, such as hepatic transporters and enzymes, are involved in this circulation, and some physiological and pathological factors can significantly affect the efficiency of biliary secretion of drugs and their metabolites, especially phase II metabolites. Each year, many papers have been published reporting biliary secretion and recirculation. This chapter provides a brief introduction to the anatomy of the liver and biliary system, the physiological function of biliary excretion, approved drugs that undergo biliary secretion, the impact of biliary excretion on ADME and PK, and the hepatic transporters involved in biliary excretion. Additionally, the chapter discusses the physiological and pathological factors that can affect biliary excretion. This chapter also summarizes the preclinical and clinical models used to investigate the biliary secretion of drugs and their metabolites. Overall, this chapter provides a comprehensive outline of the biliary excretion of drugs and drug metabolites and highlights the importance of considering biliary secretion in drug development and clinical practice.