Metabolite formation kinetics and intrinsic clearance of phenacetin, tolbutamide, alprazolam and midazolam in adenoviral P450 transfected HepG2 cells, and comparison with hepatocytes and in vivo
نویسندگان
چکیده
Unidad de Hepatología Experimental, Centro de Investigación, Hospital La Fe, Valencia, Spain (M.T.D., J.V.C., M.J.G., A.L.); CIBERehd, Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas, Fondo de Investigación Sanitaria, Spain (M.T.D., J.V.C., M.J.G.); Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Valencia, Spain (M.T.D., J.V.C.); Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, United Kingdom (D.H., J.B.H.); Unidad Mixta Hospital La Fe-Advancell, Fundación para la Investigación Hospital La Fe, Valencia, Spain (L.P.) DMD Fast Forward. Published on May 25, 2010 as doi:10.1124/dmd.110.033605
منابع مشابه
Metabolite formation kinetics and intrinsic clearance of phenacetin, tolbutamide, alprazolam, and midazolam in adenoviral cytochrome P450-transfected HepG2 cells and comparison with hepatocytes and in vivo.
Cryopreserved human hepatocytes and other in vitro systems often underpredict in vivo intrinsic clearance (CL(int)). The aim of this study was to explore the potential utility of HepG2 cells transduced with adenovirus vectors expressing a single cytochrome P450 enzyme (Ad-CYP1A2, Ad-CYP2C9, or Ad-CYP3A4) for metabolic clearance predictions. The kinetics of metabolite formation from phenacetin, ...
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Objective(s): In this study, a cocktail of probe drugs was used to assess whether lentinan could influence the activities of rat enzymes CYP3A4, CYP2D6, CYP1A2, CYP2C19, and CYP2C9 in vivo. Materials and Methods: Fourteen days after intraperitoneal injection of lentinan, rats were given an oral dose of a cocktail solution containing phenacetin, tolbutamide, omeprazole, metoprolol, and midazolam...
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