Ternant David, Paintaud Gilles
François-Rabelais University, UPRES EA 3853 Immuno-Pharmaco-Genetics of Therapeutic Antibodies, Faculty of Medicine, F 37032 Tours Cedex 1, France.
Expert Opin Biol Ther. 2005 Sep;5 Suppl 1:S37-47. doi: 10.1517/14712598.5.1.s37.
Although monoclonal antibodies (mAbs) constitute a major advance in therapeutics, their pharmacokinetic (PK) and pharmacodynamic (PD) properties are not fully understood. Saturable mechanisms are thought to occur in distribution and elimination of mAbs, which are protected from degradation by the Brambell's receptor (FcRn). The binding of mAbs to their target antigen explains part of their nonlinear PK and PD properties. The interindividual variability in mAb PK can be explained by several factors, including immune response against the biodrug and differences in the number of antigenic sites. The concentration-effect relationships of mAbs are complex and dependent on their mechanism of action. Interindividual differences in mAb PD can be explained by factors such as genetics and clinical status. PK and concentration-effect studies are necessary to design optimal dosing regimens. Because of their above-mentioned characteristics, the interindividual variability in their dose-response relationships must be studied by PK-PD modelling.
尽管单克隆抗体（mAbs）在治疗领域取得了重大进展，但其药代动力学（PK）和药效动力学（PD）特性尚未完全明确。人们认为，mAbs在分布和消除过程中存在饱和机制，且因其受到Brambell受体（FcRn）的保护而不易降解。mAbs与其靶抗原的结合解释了其部分非线性PK和PD特性。mAb PK的个体间差异可由多种因素解释，包括对生物药物的免疫反应和抗原位点数量的差异。mAbs的浓度-效应关系较为复杂，且取决于其作用机制。mAb PD的个体间差异可由遗传和临床状态等因素解释。为设计最佳给药方案，进行PK和浓度-效应研究很有必要。鉴于其上述特性，必须通过PK-PD建模研究其剂量-反应关系中的个体间差异。
