Drug-drug interactions with the involvement of macromolecules are based on either the blockade of binding sites of one drug by a competing drug, or generally, the change in binding behavior of a drug to a macromolecule in the presence of an interacting molecule, or a change in the amount of macromolecules present (e.g., an increase of drug metabolizing enzymes in the presence of enzyme-inducing drugs).
Macromolecules that are important contributors of a drug-drug interaction can be drug-metabolizing enzymes, which catalyze phase I or phase II metabolic reactions, resulting in the formation and elimination of pharmacologically active and/or inactive metabolites. Furthermore, a drug-drug interaction can take place as a result of an interaction of drugs with one or more, transporter proteins, which may be critical for the passage of drugs across biological membranes. This process is sometimes also being referred to as phase III of drug metabolism. In this particular case, the excretion of a polar—membrane impermeable—metabolite from the intracellular compartment in which it has been formed, is enhanced by binding to and subsequent transport by a membrane-bound transporter macromolecule. Finally, plasma proteins are to be mentioned, which may be viewed as a high-capacity reservoir of drugs in plasma. The significance of drugs contained within the reservoir is that they are in that state neither pharmacologically active, nor do they undergo significant clearance processes.
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