[Pharmacokinetics (PK) of mAbs].
The human Fc portion of humanized monoclonal antibodies (mAb) gives them a half-life of around 21 days, similar to that of endogenous immunoglobulin G (IgG). Neonatal Fc receptor (FcRn) plays a major role in the pharmacokinetics (PK) of mAbs. By protecting them from degradation, it is responsible for their long half-life and by allowing their transcytosis, it influences their absorption and their distribution. After subcutaneous administration, the absorption of mAbs is slow and incomplete. Most of them are still administered intravenously. Their distribution in tissues is poorly known. It seems limited and certain organs, such as the central nervous system, may be protected by FcRn. The elimination of mAbs is partly mediated by binding to their target-antigen, a mechanism that leads to dose-dependent PK. The interindividual variability in mAb PK is clinically relevant and its main known origins are demographic factors, antigen mass and immunization. Complex PK models are needed to describe satisfactorily their fate in the body and their concentration-effect relationship.
Paintaud
Gilles
G
Université François Rabelais de Tours, << Génétique, immunothérapie, chimie et cancer >>, France. paintaud@med.univ-tour.fr
D000042:Absorption; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004333:Drug Administration Routes; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D008297:Male; D051379:Mice; D010873:Pinocytosis; D011247:Pregnancy; D011961:Receptors, Fc / Q000276:immunology; D013045:Species Specificity; D014018:Tissue Distribution
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011961:Receptors, Fc; C100688:Fc receptor, neonatal