A New Model to Describe the Single-dose Pharmacokinetics of Bevacizumab and Predict Its Multiple-Dose Pharmacokinetics in Beagle Dogs
| Author | Meizhen Li | en |
| Author | Wei Qiang | en |
| Author | Zhou Wen | en |
| Author | Linling Li | en |
| Author | Lei Wang | en |
| Author | Zeneng Cheng | en |
| Issued Date | 2019-07-31 | en |
| 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. | en |
| DOI | https://doi.org/10.22037/ijpr.2019.1100716 | en |
| Keyword | Elimination | en |
| Keyword | Metabolism | en |
| Keyword | Modeling | en |
| Keyword | Monoclonal antibodies | en |
| Keyword | Simulations | en |
| Publisher | Brieflands | en |
| Title | A New Model to Describe the Single-dose Pharmacokinetics of Bevacizumab and Predict Its Multiple-Dose Pharmacokinetics in Beagle Dogs | en |
| Type | Original Article | en |