Role of Lymphatic System in Subcutaneous Absorption of Therapeutic Proteins

Abstract

Therapeutic proteins can only be injected by parenteral routes, including intravenous (IV) and subcutaneous (SC) injection. It is highly desirable for therapeutic proteins to be self‐administered SC, than by IV injection, by patient themselves, thus providing convenience for patients, and improving the quality of life and treatment adherence. Bioavailability of protein drugs after SC administration is quite variable ranging from 20% to 95%. One possible source of the variation in the bioavailability of protein drugs is the difference in presystemic catabolism of proteins in the interstitial space and/or during the transport in lymphatic vessels after SC administration. This chapter provides an overview of current knowledge of the processes of protein absorption after SC administration. In addition, the underlying mechanisms that govern the SC absorption as well as the factors that influence the SC absorption will also be discussed.

Comparison of pharmacokinetics, safety and tolerability of secukinumab administered subcutaneously using different delivery systems in healthy volunteers and in psoriasis patients

“…In the scientific literature, conflicting reports exist about the impact of site on absorption. For some biological drugs higher exposure after thigh administration than after abdominal or shoulder administration was observed, whereas for other drugs no impact of site of administration on exposure occurred . For instance, exposure of human growth hormone (22 kDa) was found to be significantly higher after s.c. injection into the abdomen than after injection into the thigh .…”

“…The PK observations as described above for the phase 1 study were confirmed in the phase 3 study in moderate to severe psoriasis patients. Serum exposure was similar after either injection of 300 mg as 2 × 1 mL in PFS or as a 16 For instance, exposure of human growth hormone (22 kDa) was found to be significantly higher after s.c. injection into the abdomen than after injection into the thigh. 17 For recombinant human erythropoietin (30 kDa), the opposite occurs, 18 although in another study with recombinant human erythropoietin, there were no significant differences between the abdomen and thigh injection sites.…”