Commentary: nonspecific protein binding versus membrane partitioning: it is not just semantics.

Nonspecific binding or sequestration results in differences between free and total drug concentrations, both in vitro and in vivo. Membrane partitioning and not protein binding is the primary mechanism of drug sequestration. Therefore, physicochemical properties, e.g., LogP can be used to predict drug sequestration in membrane and cell-based assays. The concentration of drug in a membrane is determined by the both the rate in and out of the membrane. In contrast, membrane permeability is a function of the rate in only. This commentary discusses the origins of membrane partitioning and permeability and their impact on cellular disposition.