Drugs and hepatic transporters: A review

Publication date: Available online 17 April 2019Source: Pharmacological ResearchAuthor(s): Alexander Jetter, Gerd A. Kullak-UblickAbstractThe liver is the primary organ for the metabolic degradation of xenobiotics. Transmembrane transport proteins from the ABC and the SLC families mediate the uptake of endogenous compounds and xenobiotics into the hepatocyte as well as their elimination from the cells. Multiple processes are involved. The uptake of xenobiotics in hepatocytes is mediated by organic anion transporting polypeptides (OATPs) and by organic anion and cation transporters (OATs and OCTs). The elimination of drugs and metabolites from the liver cell back to the bloodstream is accomplished mainly by multidrug resistance-associated protein 3 (MRP3) and MRP4, while the elimination towards the biliary canaliculi is mediated by several different transporters (MRP2, BCRP, MDR1 and MATE1). Since bile acids and their salts are toxic detergents for hepatocytes, they have to be eliminated efficiently. This task is accomplished by the bile salt export pump BSEP. Two further transporters, MDR3 and ATP8B1 are involved in the proper constitution of bile. All these transporters can be influenced, mainly inhibited by a number of drugs, but also by metabolites from endogenous compounds such as estrogens. Additionally, rare monogenetic diseases exist which can be explained by absence of function or dysfunction of specific hepatic transporters, such as progressive familial intrahepatic ...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research