Elimination and organ distribution of intravenously administered allogeneic and xenogeneic IgG modifications (Standard IgG, F(ab′)2-fragments andβ-propiolactone treated IgG) in dogs

Abstract

Dog IgG was produced by fractionation procedures used for the production of clinically used i.v. gammaglobulins. Chemical modification of dog IgG was done by pepsin or beta-propiolactone treatment. The intravascular half-life of beta-propiolactone IgG was 8.5 +/- 2.1 days compared to 4.5 +/- 1.6 days of pepsin treated IgG. Tissue concentrations of radioactive labelled beta-propiolactone IgG were generally higher than of pepsin digested IgG. Pepsin treated Igg was degraded to a significantly higher extent (26% of the administered radioactivity was bound to fragments smaller than 6000 MW after three days) than beta-propiolactone IgG (9% fragments after the same interval, P less than 0.001). It is concluded that the short intravascular half-life of pepsin IgG cannot be explained by increased extravascular filling, but is due to rapid degradation and excretion via the kidneys. There was no obvious difference in elimination and organ distribution between standard and beta-propiolactone IgG.

Effect of von Willebrand Factor on the Pharmacokinetics of Recombinant Human Platelet Glycoprotein Ibα-Immunoglobulin G1 Chimeric Proteins

“…The t 1/2 of GPIba-Ig/2V was also shorter than the t 1/2 of lesser potent GPIba-Ig/1V. In addition, the t 1/2 of GPIba-Ig/2V of 57 h in mice, of 84 h in rats and of 48 h in dogs were comparatively shorter to the t 1/2 of human IgG or other recombinant Fc chimeric proteins in these lab animals (4Y6, 13,14).…”