Drug depletion-time profiles in isolated hepatocytes, as well as microsomes, have become a standard method of assessing hepatic metabolic clearance in vitro. There is a previously described adaptation of the depletion approach to allow determination of hepatic uptake by transporters in addition to metabolism (Drug Metab Dispos 35:859-865, 2007). Dual incubations are performed where one set of i...

in vitro clearance (either by uptake or metabolism); CL uptake , total uptake clearance by active and passive processes; fu cell , fraction of unbound drug in the hepatocyte; k dep , Abstract Drug depletion-time profiles in isolated hepatocytes, as well as microsomes, have become a standard method of assessing hepatic metabolic clearance in vitro. Soars et al. (Drug Metab Dispos. 35: 859-65, 20...

To explore the determinants of hepatic uptake, 16 compounds were investigated with different physicochemical and disposition characteristics, including five statins, three sartans, saquinavir, ritonavir, erythromycin, clarithromycin, nateglinide, repaglinide, fexofenadine, and bosentan. Freshly isolated rat hepatocytes in suspension were used with the oil-spin method to generate kinetic paramet...