Clearance of protein drugs from the systemic circulation begins with passage across the capillary endothelium cells (9). This endothelial passage depends on the size, shape, and charge of the protein molecule and the structural and physicochemical properties of the capillaries (8). Chemical and enzymatic processes can lead to the degradation of proteins and peptides. The enzyme proteases are responsible for proteolysis, for accelerating hydrolysis and other chemical degradation processes (10).

Proteins and macromolecules are mainly cleared by renal filtration and non-p450 liver metabolism. Receptor-mediated clearance is another important mechanism of elimination for therapeutic proteins (5).

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