TY - JOUR T1 - Pharmacokinetic Modeling of the Subcutaneous Absorption of Therapeutic Proteins JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1890 LP - 1905 DO - 10.1124/dmd.114.059121 VL - 42 IS - 11 AU - Leonid Kagan Y1 - 2014/11/01 UR - http://dmd.aspetjournals.org/content/42/11/1890.abstract N2 - Subcutaneous injection is an important route of administration for therapeutic proteins that provides several advantages over other modes of parenteral delivery. Despite extensive clinical use, the exact mechanism underlying subcutaneous absorption of proteins is not completely understood, and the accuracy of prediction of absorption of biotherapeutics in humans remains unsatisfactory. This review summarizes a variety of models that have been developed for describing the pharmacokinetics of therapeutic proteins administered by subcutaneous injection, including single- and dual-pathway absorption models. Modeling of the lymphatic uptake and redistribution, absorption of monoclonal antibodies and insulin, and population analysis of protein absorption are discussed. The review also addresses interspecies modeling and prediction of absorption in humans, highlights important factors affecting the absorption processes, and suggests approaches for future development of mechanism-based absorption models. ER -