Worrell N R, Cumber A J, Parnell G D, Ross W C, Forrester J A
Biochem Pharmacol. 1986 Feb 1;35(3):417-23. doi: 10.1016/0006-2952(86)90214-5.
The pharmacokinetics and catabolism of ricin A chain, a mouse monoclonal antibody (LICR-LOND-Fib 75) and a disulphide linked conjugate of the two have been studied following their intravenous administration to normal rats. Results indicate that the conjugate was removed from the circulation much more rapidly than the antibody but less quickly than the free ricin A chain. Disappearance of the conjugate from the circulation appeared to be biphasic with an early rapid initial phase followed by a much more rapidly than the antibody but less quickly than the free ricin A chain. Disappearance of the conjugate from the circulation appeared to be biphasic with an early rapid initial phase followed by a much slower phase. The fate of a conjugate with a 125I iodide label in the antibody component was compared with that of a conjugate similarly labelled but in the ricin A chain component. The results indicate that breakdown of the conjugate involves both cleavage of the disulphide linkage and complete catabolism of the whole conjugate molecule with the release of 125I iodide. Rapid cleavage of the disulphide bond in the vasculature does not appear to be responsible for the initial rapid disappearance of the conjugate from the circulation.
在将蓖麻毒素A链、一种小鼠单克隆抗体（LICR-LOND-Fib 75）以及二者的二硫键连接缀合物静脉注射给正常大鼠后，对它们的药代动力学和分解代谢进行了研究。结果表明，缀合物从循环系统中清除的速度比抗体快得多，但比游离蓖麻毒素A链慢。缀合物从循环系统中的消失似乎呈双相，最初有一个快速的早期阶段，随后是一个比抗体慢得多但比游离蓖麻毒素A链快的阶段。缀合物从循环系统中的消失似乎呈双相，最初有一个快速的早期阶段，随后是一个慢得多的阶段。将抗体成分带有125I碘标记的缀合物的命运与蓖麻毒素A链成分同样标记的缀合物的命运进行了比较。结果表明，缀合物的分解既涉及二硫键的断裂，也涉及整个缀合物分子的完全分解代谢并释放出125I碘。血管系统中二硫键的快速断裂似乎并不是缀合物从循环系统中最初快速消失的原因。
