Transient, Tunable Expression of NTCP and BSEP in MDCKII Cells for Kinetic Delineation of the Rate-Determining Process and Inhibitory Effects of Rifampicin in Hepatobiliary Transport of Taurocholate

In predicting the hepatic elimination of compounds, extended clearance concept has proven useful. Yet, its experimental proof was scarce partly due to lack models with controlled expression transporters. Here, uptake and efflux transporters [NTCP (SLC10A1) BSEP (ABCB11), respectively] were doubly transiently expressed in MDCKII cells by electroporation-based transfection (with plasmid amount varied NTCP fixed), achieving activity levels comparable those sandwich cultured human hepatocytes. The biliary excretion for taurocholate increased proportionally level. Under same conditions, basal-to-apical transcellular displayed an initial increase, a subsequent plateau, indicating that basolateral became rate-limiting. transfected also used kinetically analyze inhibitory effects rifampicin on NTCP. obtained results showed bell-shaped profile cell-to-medium concentration ratios over range concentrations, which quantitatively captured kinetic modeling based concept. present study highlights utility transient, tunable transporter system delineating rate-determining process providing mechanistic insights into intracellular substrate accumulation.