Pharmacokinetics of teratogenic antibodies administered to rats.

Abstract

The serum levels of total and visceral yolk sac (VYS)-reactive sheep IgG have been determined following injection of a teratogenic sheep anti-VYS antiserum. After intravenous injection, levels of VYS-reactive IgG fell rapidly, with 75% of the amount in the injection removed in the first 5 min, and 90% by 60 min. By contrast, 90% or more of the total sheep IgG was still present at these times. A similar difference in clearance was seen after intraperitoneal injection, although the serum levels also reflected the presence of a pool of antiserum in the peritoneum and the simultaneous influx and efflux of IgG into and from the circulation. The clearance pattern was similar in pregnant and nonpregnant rats; it is concluded that antibodies against VYS-specific antigens comprise a very small fraction of VYS-reactive antibodies in the antiserum. ELISA and Western blot analysis indicated extensive cross-specificity with antigens present in rat tissues other than the VYS. Similar teratogenic effects were observed after intravenous or intraperitoneal injection of the antiserum at 8.5 days of gestation; we conclude that the proximal effect likely begins within the period immediately after the injection. The results are also considered within the context of published reports that the VYS shows structural and functional damage for several days after intraperitoneal administration of antiserum at 8.5 days.