Abstract
AbstractA remarkable feature of the disposition of polypeptide hormones is the contribution of specific binding sites (receptors) on the cell-surface to their clearance in the body. Receptor-mediated endocytosis (RME) is now well recognized as a polypeptide clearance system. In addition, drug targeting utilizing RME is expected to have promise as a drug delivery system (DDS) to carry some drug specifically into the target cell expressing receptors on its plasma membrane. Therefore, it is important to analyze the RME process kinetically, both to clarify the pharmacokinetics of polypeptide itself and to estimate the efficiency of drug targeting via polypeptide receptors. We have been studying the hepatic handling of epidermal growth factor (EGF) and hepatocyte growth factor (HGF) using perfused rat liver, isolated rat hepatocytes, and primary cultured rat hepatocytes. Kinetic analysis of hepatic clearance of EGF enabled us to determine the kinetic parameters for the construction of a kinetic model for RME. ...
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