title: A novel pharmacokinetic model based on the complex elimination of monoclonal antibodies for bevacizumab pharmacokinetic study in rabbits.
abstract: Monoclonal antibodies (mAbs) complex pharmacokinetic (PK) properties including a nonlinear pharmacokinetics and a significant variation in individual PK process cannot be appropriately described by classic PK models, probably derived form a poor understanding of the complex elimination of mAbs. In this study, a novel PK model based on mAbs' complex drug elimination was established. Subsequently, this new model was used to fit bevacizumab plasma concentration data from PK rabbits, and the outcomes of model fitting were compared with those came from a fit with classic models. In addition, the variations existing in the parameters set in the new model were analyzed. As a result, this novel model reasonably described the single-dose PK profiles of bevacizumab in rabbits, and its fitting efficiency was greatly improved compared with those fitted with classic PK models in terms of the weighted residual sum of squares. Moreover, the variations existing in the new model's parameters CA(antibody) and K0 could reasonably explain the individual variations of bevacizumab's PK profiles. In conclusion, the novel model reasonably explained the elimination of bevacizumab, and exhibited a potential as a useful tool for the PK studies of bevacizumab and other mAbs in practice.
authors.affiliation: Research Institute of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Research Institute of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Ji
authors.affiliation: Research Institute of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, China.
authors.forename: Meizhen
authors.initials: M
authors.lastname: Li
authors.affiliation: Research Institute of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, China. Electronic address: chengzn@csu.edu.cn.
authors.forename: Zeneng
authors.initials: Z
authors.lastname: Cheng
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D000818:Animals; D000068258:Bevacizumab / Q000493:pharmacokinetics*; D008954:Models, Biological; D059748:Proteolysis; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
keywords: Bevacizumab; Estimation; Monoclonal antibody; Nonlinear elimination; Pharmacokinetics