Fig. 8.

Comparison of the uptake affinity (A), active uptake clearance (B), and passive diffusion clearance (C) of seven OATP substrates in rat and human hepatocytes. K_{m, u}, CL_{active, u}, and P_{diff, u} estimates in rat hepatocytes were obtained from full kinetic experiments for all drugs. Data represent the mean ± S.D. of three experiments. K_{m, u} and P_{diff, u} in human hepatocytes were obtained from full kinetic experiments in donor HU4122, with the exception of rosuvastatin and repaglinide, for which full kinetic experiments were conducted in all three human hepatocyte donors. CL_{active, u} in humans is the mean ± S.D. of estimates obtained from the full kinetic experiment in donor HU4122 and extrapolated from experiments conducted at 1 μM in donors HU4199 and HU8089. In A and B, ——, line of unity. – – –, 2-fold difference. In C, ——, line of best fit between LogD_7.4 and the passive diffusion clearances generated in human hepatocytes. ●, data generated in human hepatocytes; ○, data obtained in rat hepatocytes. 1, pitavastatin; 2, pravastatin; 3, telmisartan; 4, repaglinide; 5, rosuvastatin; 6, valsartan; 7, bosentan.