DIFFERENTIAL KINETICS FOR IMMUNONEUTRALIZATION OF CIRCULATING GASTRIN BY GASTRIN MONOCLONAL-ANTIBODY AND ITS FAB(1) FRAGMENT IN RATS

The kinetics of gastrin immunoneutralization were studied in rats treated with a mouse monoclonal IgG antibody to gastrin (CURE GAS 93) and with the Fab(1) prepared from this antibody. Clearance studies using specific ELISA measurements of serum IgG or Fab determined the T-1/2 for IgG as 59.3 +/- 3.5 h and for Fab(1) as 7.3 +/- 0.7 h. Gastrin was immunoneutralized in rats for up to 16 days using alternate day IP injections of anti-gastrin immunoglobulin. Gastric acid secretion stimulated by gastrin-17, but not histamine, was inhibited 48 h after the last dose of antibody, indicating specific inhibition of gastrin. Peak serum levels of antibody were observed 8 h after IP administration and indicated an estimated 70% absorption of the administered dose. Fab(1) fragments completely blocked gastric acid secretion stimulated by gastrin-17, but not histamine, 4 h after IV administration; however, this effect was not observed 24 h after administration. This study demonstrates the effectiveness of chronic immunoneutralization of gastrin and defines effective period of immunoneutralization for intact IgG and for the Fab(1) fragment.