Contribution of various organs to the elimination of endogenous IgG (Immunoglobulin G)

Range skin tissue 33%: muscle tissue 24%: liver tissue 16%: gut tissue 12% %
Organism Mouse Mus musculus
Reference Keizer RJ, Huitema AD, Schellens JH, Beijnen JH. Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010 Aug49(8):493-507. doi: 10.2165/11531280-000000000-00000. p.498 right column bottom paragraphPubMed ID20608753
Primary Source Garg A, Balthasar JP. Physiologically-based pharmacokinetic (PBPK) model to predict IgG tissue kinetics in wild-type and FcRn-knockout mice. J Pharmacokinet Pharmacodyn 2007 34: 687-709PubMed ID17636457
Method Primary source abstract: "In the present work, a physiologically-based pharmacokinetic (PBPK) model has been developed to characterize and predict IgG disposition in plasma and in tissues. The model includes nine major compartments, connected in an anatomical manner, to represent tissues known to play a significant role in IgG disposition. Each tissue compartment was subdivided into vascular, endosomal and interstitial spaces."
Comments P.498 right column bottom paragraph: "Because of their molecular size, mAbs are not excreted into urine but are metabolized to peptides and amino acids that can be re-used in the body for de novo synthesis of proteins or are excreted by the kidney. Metabolism of endogenous IgG occurs in various body tissues and in plasma. Using physiologically based pharmacokinetic modelling, the contribution of various organs to the elimination of endogenous IgG was estimated to be 33%, 24%, 16% and 12% for skin, muscle, liver and gut tissue, respectively [primary source]. The elimination routes of mAbs are not well documented, and several mechanisms are reported to be involved. These mechanisms are discussed below and include proteolysis by the liver and the reticuloendothelial system (RES), target-mediated elimination and nonspecific endocytosis."
Entered by Uri M
ID 112410