Author/Authors :
Li, Meizhen Research Institute of Drug Metabolism and Pharmacokinetics - School of Pharmaceutical Sciences - Central South University, Changsha, Hunan, China , Qiang, Wei Research Institute of Drug Metabolism and Pharmacokinetics - School of Pharmaceutical Sciences - Central South University, Changsha, Hunan, China , Wen, Zhou Research Institute of Drug Metabolism and Pharmacokinetics - School of Pharmaceutical Sciences - Central South University, Changsha, Hunan, China , Li, Linling Research Institute of Drug Metabolism and Pharmacokinetics - School of Pharmaceutical Sciences - Central South University, Changsha, Hunan, China , Wang, Lei Research Institute of Drug Metabolism and Pharmacokinetics - School of Pharmaceutical Sciences - Central South University, Changsha, Hunan, China , Cheng, Zeneng Research Institute of Drug Metabolism and Pharmacokinetics - School of Pharmaceutical Sciences - Central South University, Changsha, Hunan, China
Abstract :
Complex pharmacokinetic (PK) properties including nonlinear elimination were encountered
by some monoclonal antibodies (mAbs), and classic compartment models sometimes failed to
appropriately describe those properties. In this work, a new model was built on a comprehensive
analysis of the complex elimination of mAbs. This new model was firstly utilized to fit with the
single-dose plasma concentration data of bevacizumab in beagle dogs receiving an intravenous
administration of 2.5 mg/kg bevacizumab. Then, the optimal PK parameters from fitting with
the single-dose PK data were employed into the multiple-dose mathematical expressions to
predict bevacizumab’s multiple-dose PK profiles. One-compartment model recommended as
the optimal classic model by DAS 2.0 software was set as a control. As a result, new model
fitted better with the single-dose PK profiles of bevacizumab with smaller weighted residual
sum of squares and higher fitting degree compared with the classic model. Importantly, new
model also accurately predicted the multiple-dose PK profiles of bevacizumab and performed
well at the single-to-multiple transition. In conclusion, the new model reasonably explained
the complex elimination of bevacizumab, and it might play a big role in the PK studies of
bevacizumab and other mAbs.
Keywords :
Simulations , Monoclonal antibodies , Modeling , Elimination , Metabolism
