Pharmakokinetische Besonderheiten von therapeutischen Antikörpern

Abstract

Because of their high molecular weight and their highly hydrophilic character, therapeutic antibodies behave differently in terms of absorption, distribution and elimination compared to conventional drugs. Also, their pharmacokinetic profile varies significantly among individuals. After subcutaneous administration, antibodies are absorbed via the lymphatic system and become systemically bioavailable with some delay. The physicochemical properties of the molecules hinder their distribution from the bloodstream into the tissue. Elimination occurs by proteolysis in various organs (skin, muscle, liver), but mainly within the reticuloendothelial system. Also relevant is the elimination through target antigens (especially in the case of cell-bound target antigens) as well as a recycling process through binding to the neonatal Fc receptor that provides protection from lysosomal degradation. Depending on the immunogenicity of the therapeutic antibody and the individual immune response, neutralizing antibodies can develop. Pharmacokinetic conditions can be optimized by coadministration of, for example, methotrexate. Moreover, risk factors for the loss of immunological tolerance, such as on-demand therapy or elective switching of therapeutic antibodies, should be avoided.