Impact of liver diseases and pharmacological interactions on the transportome involved in hepatic drug disposition
Biochem Pharmacol. 2024 Mar 23:116166. doi: 10.1016/j.bcp.2024.116166. Online ahead of print.ABSTRACTThe liver plays a pivotal role in drug disposition owing to the expression of transporters accounting for the uptake at the sinusoidal membrane and the efflux across the basolateral and canalicular membranes of hepatocytes of many different compounds. Moreover, intracellular mechanisms of phases I and II biotransformation generate, in general, inactive compounds that are more polar and easier to eliminate into bile or refluxed back toward the blood for their elimination by the kidneys, which becomes crucial when the biliary route is hampered. The set of transporters expressed at a given time, i.e., the so-called transportome, is encoded by genes belonging to two gene superfamilies named Solute Carriers (SLC) and ATP-Binding Cassette (ABC), which account mainly, but not exclusively, for the uptake and efflux of endogenous substances and xenobiotics, which include many different drugs. Besides the existence of genetic variants, which determines a marked interindividual heterogeneity regarding liver drug disposition among patients, prevalent diseases, such as cirrhosis, non-alcoholic steatohepatitis, primary sclerosing cholangitis, primary biliary cirrhosis, viral hepatitis, hepatocellular carcinoma, cholangiocarcinoma, and several cholestatic liver diseases, can alter the transportome and hence affect the pharmacokinetics of drugs used to treat these patients. Moreover, hepatic ...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Jose J G Marin Candela Cives-Losada Rocio I R Macias Marta R Romero Rebeca P Marijuan Nazaret Hortelano-Hernandez Kevin Delgado-Calvo Carmen Villar Jesus M Gonzalez-Santiago Maria J Monte Maitane Asensio Source Type: research
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