[Frontline in Biliary Excretion of Drugs and Their Evaluation Systems].

Abstract

In vitro studies using human liver-derived cell lines have been investigated as a method for evaluating biliary excretion of drugs. In several of these studies, it has been shown that a capillary bile duct-like network is formed by culturing liver-derived cells in two/three-dimensional culture (2D and/or 3D) using fluorescent substrates that are excreted in bile. Recently, it was reported that bile duct epithelial-like cells (BECs) capable of long-term proliferation can be obtained by establishing organoids from primary human hepatocytes. We therefore cultured these bile duct epithelial-like organoids on an insert in 2D culture and investigated the biliary excretory capacity of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated protein2 (MRP2) substrates. We found that all drugs were significantly excreted into the bile duct lumen side. In the first half of this review, the current state of knowledge on biliary excretion of drugs is summarized, and in the second half, the latest findings, including our presentation at the Annual Meeting Symposium of The Pharmaceutical Society of Japan in 2024, are described, focusing on the evaluation system for biliary excretion of drugs.