Evidence of drug-drug interactions through uptake and efflux transport systems in rat hepatocytes: implications for cellular concentrations of competing drugs.
- 2013-05-28
Published in:
- Drug metabolism and disposition: the biological fate of chemicals. - 2013
Animals
Biological Transport
Drug Interactions
Hepatocytes
Male
Meglumine
Multidrug Resistance-Associated Proteins
Organic Anion Transporters
Organometallic Compounds
Rats
Rats, Sprague-Dawley
Rifampin
English
For drugs with hepatobiliary transport across hepatocytes, the interplay between uptake and efflux transporters determines hepatic concentrations of drugs, but the evolution over time of these concentrations is difficult to measure in humans other than with magnetic resonance imaging contrast agents in the liver. Gadobenate dimeglumine (BOPTA) is a contrast agent used in liver magnetic resonance imaging that enters into human hepatocytes through organic anion transporting polypeptides (OATP) and exits unchanged into bile through the multiple resistance-associated protein 2 (MRP2). Rifampicin (RIF) is transported by the same membrane proteins and may compete with BOPTA for hepatic uptake. Simultaneous drug-drug interactions through uptake and efflux transport systems in hepatocytes according to the cellular concentrations of competing drugs were never investigated. In perfused rat liver preparations, we demonstrate how the drug-drug interactions through transporters determine cellular concentrations of the competing drugs BOPTA and RIF, and we show that the cellular concentrations by modulating transport through membranes regulate the rat Oatp-Mrp2 interplay. Moreover, drug interactions through transporters change greatly over time.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1124/dmd.113.051870
- PMID 23708009
- Persistent URL
- https://fredi.hepvs.ch/global/documents/21240
Statistics
Document views: 14
File downloads:
- Full-text: 0