Pharmacokinetics of teratogenic antibodies administered to rats.
Pharmacokinetics of teratogenic antibodies administered to rats.
复制标题
给予大鼠致畸抗体的药代动力学。
DOI：
10.1002/tera.1420520504
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
LLoyd,JB
中科院分区：
文献类型：
--
作者：
Fawcett,LB;Beckman,DA;Fawcett,PT;Brent,RL;LLoyd,JB
在注射致畸性绵羊抗VYS抗血清后，测定了总卵黄囊（VYS）反应性绵羊IgG和内脏卵黄囊（VYS）反应性绵羊IgG的血清水平。静脉注射后，VYS反应性IgG水平迅速下降，在前5分钟内去除了注射液中75%的量，60分钟时去除了90%。相比之下，在这些时间内仍存在90%或更多的总羊IgG。腹膜内注射后观察到类似的清除率差异，尽管血清水平也反映了腹膜中存在抗血清池以及IgG同时流入和流出循环。妊娠和非妊娠大鼠的清除模式相似;可以得出结论，抗VYS特异性抗原的抗体在抗血清中占VYS反应性抗体的极小部分。ELISA和Western印迹分析表明，与除VYS外的大鼠组织中存在的抗原具有广泛的交叉特异性。在妊娠8.5天静脉或腹膜内注射抗血清后观察到类似的致畸作用;我们得出结论，近端效应可能在注射后立即开始。在已发表报告的背景下也考虑了这些结果，即在第8.5天腹膜内给予抗血清后，VYS显示出持续数天的结构和功能损伤。© 1995 Wiley利斯公司
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 introperitoneal 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. © 1995 Wiley‐Liss, Inc.