ABSTRACT

Drug-drug interactions involving the membrane transport process do not occur when drugs pass through the plasma membrane by passive diffusion, a nonsaturable route. Also, it is possible to estimate the membrane permeability by measuring the physicochemical properties of the drugs, which enables us to predict drug disposition in silico. Transporters mediate the membrane transport of a great number of drugs and endogenous compounds. Since the number of binding sites of transporters for drugs is limited, the transport process is saturated at concentrations higher than the Km value. Also, when drugs share the same binding sites of transporters, drug-drug interactions may occur, depending on their pharmacokinetic properties. These may alter the drug disposition and/or its pharmacological effects. In addition, it is possible that there are species differences in the affinity and/or maximum transport velocity of drugs and in the transporter responsible for the drugs' disposition. Therefore, it may be difficult in some cases to predict drug-drug interactions in humans from in vitro transport experiments using animal models.