Pharmacokinetic modeling and quantitative prediction of subcutaneous absorption of antibody-based therapeutics – An update

A significant advancement has been made in recent years in understanding subcutaneous (SC) absorption of biologics. Still, the accurate prediction of human SC absorption of antibody-based therapeutics remains an unmet need. A review article published in 2014 (Kagan. Pharmacokinetic Modeling of the Subcutaneous Absorption of Therapeutic Proteins. Drug Metabolism and Disposition 11: 1890-1905) - summarized and categorized published pharmacokinetic (PK) models for describing SC absorption of biologics. This review provides a contemporary update and extension of the previous review based on the considerable progress in the field over the last decade with the main focus on antibody-based therapeutics. Narrative analysis of approaches utilized in clinical population PK models for describing absorption of SC products approved by the FDA was performed. Moreover, we summarized advancement in development of physiologically-based pharmacokinetic models for SC absorption (SC-PBPK), hyaluronidase-facilitated SC delivery, physics-based models of SC injection site and lymphatics, and other mechanistic models. Lastly, other quantitative approaches aimed at predicting SC absorption in humans based on in-silico, in-vitro, and in-vivo preclinical and clinical data were described. The manuscript provides a valuable tool for all professionals engaged in the development, advancement, and clinical translation of biologics, including antibody-based therapeutics.