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...

Department of Pharmacology, Clinical Pharmacology, University of Cologne, Germany (D.T.S., U.F., D.F., O.D., A.J., J.S.); Institute of Medical Statistics, Informatics and Epidemiology University of Cologne, Germany (M.H.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (A.J.); Department of Pharmacology of Natural Products and Clinical Pharma...

INTRODUCTION The possibility that variation in packaging and pill appearance may reduce adherence is a reason for concern, especially for chronic diseases. The objectives of the study were to quantify the extent of switches between generic antidiabetics and to verify whether switching between different products of the same substance affects adherence. MATERIALS AND METHODS All elderly residen...