Liver retention clearing agents (LRCAs) and the use thereof are discussed. LRCAs are composed of a hepatic clearance directing component which directs the biodistribution of a LRCA-containing construct to hepatic clearance; a binding component which mediates binding of the LRCA to a compound for which rapid hepatic clearance is desired; a liver retention component which diminishes access of binding component-containing metabolites to target sites; and a structural component to provide a scaffold for the other components.