Analysis of sinusoidal drug uptake transporter activities in primary human hepatocytes

Abstract

Hepatic drug transporters play an important role in pharmacokinetics and drug–drug interactions. Among these membrane transporters, the sodium taurocholate cotransporting polypeptide (NTCP/SLC10A1), the organic anion transporting polypeptides (OATPs) 1B1 (SLCO1B1), 1B3 (SLCO1B3) and 2B1 (SLCO2B1), the organic anion transporter 2 (OAT2/SLC22A7) and the organic cation transporter 1 (OCT1/SLC22A1) are likely major ones, notably mediating sinusoidal uptake of various drugs or endogenous compounds, like bile acids, from blood into hepatocytes. Studying putative interactions of drugs, including those in development processes, with these transporters is an important issue. For this purpose, cultured human hepatocytes, that exhibit functional expression of NTCP, OATPs, OAT2 and OCT1, are considered as a relevant in vitro cellular model. This chapter describes a method allowing to accurately analyze NTCP, OATP, OAT2 and OCT1 transport activities in primary human hepatocyte cultures, which can be applied to the determination of potential interactions of drugs with these hepatic uptake transporters.