Title of article
A New Model to Describe the Single-dose Pharmacokinetics of Bevacizumab and Predict Its Multiple-Dose Pharmacokinetics in Beagle Dogs
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
Pages
9
From page
1147
To page
1155
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
Journal title
Astroparticle Physics
Serial Year
2019
Record number
2487119
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