Extrapolation of In Vivo Hepatic Clearance from In Vitro Uptake Clearance by Suspended Human Hepatocytes for Anionic Drugs with High Binding to Human Albumin: Improvement of In Vitro-to-In Vivo Extrapolation by Considering the “Albumin-Mediated” Hepatic Uptake Mechanism on the Basis of the “Facilitated-Dissociation Model”

• Published in: Drug metabolism and disposition Vol. 47; no. 2; pp. 94 - 103
• Main Authors: Kim, Soo-Jin, Lee, Kyeong-Ryoon, Miyauchi, Seiji, Sugiyama, Yuichi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2019; American Society for Pharmacology and Experimental Therapeutics, Inc
• Subjects: Albumin; Anions - metabolism; Binding; Biocompatibility; Cell surface; Clearances; Dialysis; Drugs; Equilibrium dialysis; Extrapolation; Hepatobiliary Elimination; Hepatocytes; Hepatocytes - metabolism; Human serum albumin; Humans; Liver; Mathematical models; Models, Biological; Organic Anion Transporters - metabolism; Organic anion transporting polypeptide; Pharmaceutical Preparations - metabolism; Plasma - metabolism; Protein Binding; Serum albumin; Serum Albumin, Human - metabolism; Substrates; IVIVE; fp; OATP; fu; PSinf; R; CLvivoh,u,int,all; SF; RSV; PRV; HSA; PSb,inf; PSu,inf; PSu,inf (+)

We investigated whether human serum albumin (HSA) in suspended human hepatocytes would affect the uptake clearance of anionic drugs with high binding to HSA and improve the extrapolation of in vivo hepatic clearance from in vitro uptake clearance by the hepatocytes via the “albumin-mediated” hepatic...