PHARMACOKINETICS OF TERATOGENIC ANTIBODIES ADMINISTERED TO RATS

The serum levels of total and visceral yolk sac (VYS)-reactive sheep I gG have been determined following injection of a teratogenic sheep ant i-VYS antiserum. After intravenous injection, levels of VYS-reactive I gG fell rapidly, with 75% of the amount in the injection removed in th e first 5 min, and 90% by 60 min. By contrast, 90% or more of the tota l 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 peri toneum and the simultaneous influx and efflux of IgG into and from the circulation. The clearance pattern was similar in pregnant and nonpre gnant rats; it is concluded that antibodies against VYS-specific antig ens comprise a very small fraction of VYS-reactive antibodies in the a ntiserum. ELISA and Western blot analysis indicated extensive cross-sp ecificity with antigens present in rat tissues other than the VYS. Sim ilar teratogenic effects were observed after intravenous or intraperit oneal 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 contex t of published reports that the VYS shows structural and functional da mage for several days after intraperitoneal administration of antiseru m at 8.5 days. (C) 1995 Wiley-Liss, Inc.