Figure 5.

Human sandwich-cultured hepatocytes (SCH) were incubated for 10 min at 37 °C with 0.5 µCi/ml ^99mTc–mebrofenin in standard (cells + bile) or Ca⁺-free (cells) HBSS (using B-CLEAR technology) alone and with various concentrations of ritonavir in SCH from three separate donors, in triplicate. (a) ^99mTc–mebrofenin accumulation and biliary excretion index (BEI) in cells + bile (closed bars) and cells (open bars) in the presence of increasing concentrations of extracellular ritonavir. ^99mTc–mebrofenin BEI values (above the bars) represent mean data. (b) Ritonavir accumulation in hepatocytes (Ca²⁺-free HBSS) when coadministered with ^99mTc–mebrofenin, represented as intracellular total concentration (C_cell,total), as described in Methods section. ^99mTc–mebrofenin and ritonavir accumulation data are represented as mean ± SEM of three separate donors in triplicate (5 µmol/l data are mean ± range of two donors, in triplicate).