Open Access Research article

Pharmacokinetics and pharmacodynamics of VEGF-neutralizing antibodies

Stacey D Finley*, Marianne O Engel-Stefanini, PI Imoukhuede and Aleksander S Popel

Author Affiliations

Department of Biomedical Engineering, Johns Hopkins University, School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA

For all author emails, please log on.

BMC Systems Biology 2011, 5:193  doi:10.1186/1752-0509-5-193

Published: 21 November 2011

Additional files

Additional file 1:

Chemical reactions and equations for the compartment model of VEGF distribution in the body. This file also contains a glossary of terms used in the model equations.

Format: DOC Size: 419KB Download file

This file can be viewed with: Microsoft Word Viewer

Open Data

Additional file 2:

We investigated how the kinetic parameters governing NRP2 binding to VEGF165 and coupling to VEGFR1 and VEGFR2 influenced the steady-state concentration of free VEGF in the body. A, Effect of VEGF165 binding to NRP2; squares and triangles indicate lower and upper values of kon, respectively, taken from literature. B, Effect of NRP2 coupling to VEGF165/VEGFR2. C, Effect of VEGF165/NRP2 coupling to VEGFR2. D, Effect of NRP2 coupling to VEGFR1. In all panels, gray circles indicate baseline values taken from NRP1 interactions.

Format: PDF Size: 69KB Download file

This file can be viewed with: Adobe Acrobat Reader

Open Data

Additional file 3:

Comparison of the concentration of free VEGF in the tumor interstitial space calculated from experimental data and based on model predictions.

Format: DOC Size: 33KB Download file

This file can be viewed with: Microsoft Word Viewer

Open Data

Additional file 4:

VEGF distribution following a single intravenous injection of 10 mg/kg of anti-VEGF given at time 0. A, normal tissue, B, blood, and C, tumor.

Format: PDF Size: 51KB Download file

This file can be viewed with: Adobe Acrobat Reader

Open Data

Additional file 5:

The concentration profiles for A, free VEGF; B, free anti-VEGF; and C, the VEGF/anti-VEGF complex are predicted as the lymphatic flow rate from the normal tissue to the blood was varied. From top to bottom: normal tissue, blood, and tumor. The lymph flow rate influences the concentration of the anti-VEGF and VEGF/anti-VEGF complex. Legend in A applies to all panels; bold in the legend indicates the parameter value used in the current model.

Format: PDF Size: 125KB Download file

This file can be viewed with: Adobe Acrobat Reader

Open Data

Additional file 6:

The concentration of the VEGF/anti-VEGF complex in the body following anti-VEGF treatment is predicted as properties of the anti-VEGF are varied. A, Effect of microvascular permeability to anti-VEGF between the normal tissue and blood. B, Effect of microvascular permeability to anti-VEGF between the tumor and blood. C, Effect of clearance rate of anti-VEGF. D, Effect of anti-VEGF binding affinity to VEGF. From top to bottom: normal tissue, blood, and tumor. Bold in the legend indicates parameter value used in the current model.

Format: PDF Size: 121KB Download file

This file can be viewed with: Adobe Acrobat Reader

Open Data

Additional file 7:

The concentration of free anti-VEGF in the body following anti-VEGF treatment is predicted as properties of the anti-VEGF are varied. A, Effect of microvascular permeability to anti-VEGF between the normal tissue and blood. B, Effect of microvascular permeability to anti-VEGF between the tumor and blood. C, Effect of clearance rate of anti-VEGF. D, Effect of anti-VEGF binding affinity to VEGF. From top to bottom: normal tissue, blood, and tumor. Bold in the legend indicates parameter value used in the current model.

Format: PDF Size: 117KB Download file

This file can be viewed with: Adobe Acrobat Reader

Open Data