New insights on the pharmacokinetics of venoms and antivenoms

Abstract

The development of enzyme-linked immunosorbent assays (ELISA) for venoms and antivenoms with high sensitivity has enabled to characterize pharmacokinetics (PK) of venoms and antivenoms, which in turn allowed modeling their absorption, distribution, and elimination, as well as the adequacy of different therapeutic regimes. Pharmacokinetics is the branch of pharmacology dealingwith absorption, distribution, and elimination of drugs in the body; it is fundamental to determine the dose and dosing scheme of a drug. ELISA studies provided evidence indicating that antivenoms (in spite of their large molecular size) are quickly and actively extravasated from blood to tissues. ELISA studies have also enabled to show that heterologous antibodies induce production of antibodies able to interact with antivenoms, modifying their PK and reducing their effectiveness. This has been confirmed using high-resolution deconvolution fluorescence microscopy (HRDFM) of fluorescently labeled antivenoms. HRDFM has also provided evidence showing a complex distribution of antivenoms in the body and has shown that mammalian immunoglobulins (IgG) are transported very differently in the body than avian IgYs, which suggests they must have different PK.