Functional ATP-binding cassette drug efflux transporters in isolated human and rat hepatocytes significantly affect assessment of drug disposition.

Dmd054528 448..458

Freshly isolated hepatocytes are considered the gold standard for in vitro studies of hepatic drug disposition. To ensure a reliable supply of cells, cryopreserved human hepatocytes are often used. ABC-superfamily drug efflux transporters are key elements in hepatic drug disposition. These transporters are often considered lost after isolation of hepatocytes. In the present study, the expressio...

Prediction of in vivo rat biliary drug clearance from an in vitro hepatocyte efflux model.

Well-established techniques are available to predict in vivo hepatic uptake and metabolism from in vitro data, but predictive models for biliary clearance remain elusive. Several studies have verified the expression and activity of ATP-binding cassette (ABC) efflux transporters central to biliary clearance in freshly isolated rat hepatocytes, raising the possibility of predicting biliary cleara...

ATP-Binding Cassette Efflux Transporters and Passive Membrane Permeability in Drug Absorption and Disposition

Expression of Drug Pump Protein MRP2 in Lipopolysaccharide-Treated Rats and Its Impact on the Disposition of Acetaminophen

The drug pump protein MRP2 is a membrane drug efflux transporter widely distributed in normal and tumor tissues. Its role is thought to be crucial for the disposition of many drugs and their substrates in different tissues. In this study, we aimed to examine the effects of systematic inflammation induced by lipopolysaccharide (LPS) on the expression and function of this transporter in rats. Jug...

Expression of Drug Pump Protein MRP2 in Lipopolysaccharide-Treated Rats and Its Impact on the Disposition of Acetaminophen

The drug pump protein MRP2 is a membrane drug efflux transporter widely distributed in normal and tumor tissues. Its role is thought to be crucial for the disposition of many drugs and their substrates in different tissues. In this study, we aimed to examine the effects of systematic inflammation induced by lipopolysaccharide (LPS) on the expression and function of this transporter in rats. Jug...