Elimination Pathways of Biologics

In general, biologics are metabolized into small peptide fragments or amino acids that are ready for renal excretion or for recycling into protein synthesis. Metabolism happens mainly via intracellular lysosomal proteolytic degradation which occurs throughout the entire body. The traditional elimination pathways of small drugs by liver and bile is less common for biologics, although they may occur. Renal excretion is notably limited, due to the inability of the kidneys to filter large molecules. Consequently, dosing regimen adjustment with biologics is less of a concern in renal failure, however with some exceptions.

Biologics are eliminated from the body by two general pathways: metabolism/catabolism and excretion. Catabolism refers to the non-specific enzymatic degradation, for example by peptidases. This accounts for poor oral bioavailability of biologics and oral formulation is currently ruled out from consideration. Metabolism occurs mainly via intracellular lysosomal proteolytic degradation which could be either specific or non-specific. Renal excretion is limited because of molecular size being not conducive for glomerular filtration. Dosing regimen adjustment with biologics is less of a concern in renal failure, however with some exceptions (e.g., rh-IL10). It should be also noted that hepatocyte uptake can happen through carrier-mediated transport or carrier-mediated endocytosis, which constitutes part of the metabolic pathways.