Hepatic Barrier
The Liver Package
SOLVO offers a wide range of liver-specific assays to study hepatic uptake, the interaction of test compounds with liver transporters or to test the effect of test compounds on the disposition of other drugs or that of physiological compounds, like bile salts. Test compounds can be studied in isolated, specific transporter assays. All relevant hepatic transporters are available at SOLVO. Furthermore SOLVO offers more complex systems, like double transfected cell lines, and hepatic uptake studies using primary human or rat hepatocytes to study interaction in a physiologically more relevant environment. In vivo studies in bile cannulated rats are also available to test the effect of transporters on the biliary excretion of test compounds or test their effect on the transport of other drugs or physiological compounds.
All methods are available either separately or in combination, as a package.
About the Liver Barrier
Drug disposition is the net result of the different processes involved in drug uptake, metabolism and excretion. Members of the uptake transporter family, as well as certain efflux transporters and drug metabolizing enzymes are key players in drug disposition.
The screening of the interaction of test drugs, nutrients and other molecules with hepatic efflux and uptake transporters is an excellent way to study their hepatobiliary DMPK and to lower the risk of hepatotoxicity caused by bile acid retention. Several of the basolateral and apical transporters for bile acids are thought to be targets of drugs that induce cholestasis.
Figure 1. Transporters in human hepatocytes
To gain information on biliary clearance, BSEP, MRP2, BCRP, P-gpand MATE1 transporter interactions need to be investigated. For the detection of possible interactions on the basolateral membrane, MRP3, MRP4 and MRP5 efflux transporters should be considered.
The involvement of human uptake transporters in the hepatic transport processes is just as crucial as the role of the efflux transporters. When investigating hepatobiliary disposition, it is highly recommended to perform screens for NTCP, OATP-C (OATP2 / OATP1B1), OATP8 (OATP1B3), OATP-B (OATP2B1), OAT2, OCT1 and OCT3. In case of rat pharmacokinetic studies, Rat Ntcp, rat Oatp1 (Oatp1a1), rat Oatp2 (Oatp1a4), rat Oatp4 (Oatp1b2), rat Oat2 and ratOct1 should be considered
Figure 2. Transporters in murine hepatocytes
For more information on our service, please click here.
