Paintaud Gilles
Université François Rabelais de Tours, << Génétique, immunothérapie, chimie et cancer >>, France.
Med Sci (Paris). 2009 Dec;25(12):1057-62. doi: 10.1051/medsci/200925121057.
The human Fc portion of humanized monoclonal antibodies (mAb) gives them a half-life of around 21 days, similar to that of endogenous immunoglobulin G (IgG). Neonatal Fc receptor (FcRn) plays a major role in the pharmacokinetics (PK) of mAbs. By protecting them from degradation, it is responsible for their long half-life and by allowing their transcytosis, it influences their absorption and their distribution. After subcutaneous administration, the absorption of mAbs is slow and incomplete. Most of them are still administered intravenously. Their distribution in tissues is poorly known. It seems limited and certain organs, such as the central nervous system, may be protected by FcRn. The elimination of mAbs is partly mediated by binding to their target-antigen, a mechanism that leads to dose-dependent PK. The interindividual variability in mAb PK is clinically relevant and its main known origins are demographic factors, antigen mass and immunization. Complex PK models are needed to describe satisfactorily their fate in the body and their concentration-effect relationship.
人源化单克隆抗体（mAb）的人Fc部分使其半衰期约为21天，与内源性免疫球蛋白G（IgG）相似。新生儿Fc受体（FcRn）在mAb的药代动力学（PK）中起主要作用。通过保护它们不被降解，它决定了它们的长半衰期，并且通过允许它们的转胞吞作用，它影响它们的吸收和分布。皮下给药后，mAb的吸收缓慢且不完全。大多数mAb仍通过静脉给药。它们在组织中的分布知之甚少。其分布似乎有限，某些器官，如中枢神经系统，可能受到FcRn的保护。mAb的消除部分是通过与靶抗原结合介导的，这是一种导致剂量依赖性PK的机制。mAb PK的个体间变异性具有临床相关性，其主要已知来源是人口统计学因素、抗原量和免疫接种。需要复杂的PK模型来令人满意地描述它们在体内的转归及其浓度-效应关系。
