Wu2017 - Murine Bevacizumab PK model

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Model Identifier
MODEL2003030003
Short description
<notes xmlns="http://www.sbml.org/sbml/level2/version4"> <body xmlns="http://www.w3.org/1999/xhtml"> <p>This is the first report evaluating the use of fluorescent imaging to determine the pharmacokinetics, lymphatic uptake, and bioavailability of a near-infrared dye-labeled antibody conjugate. Model is encoded by Matthew Roberts and submitted to BioModels by Krishna Tiwari</p> </body> </notes>
Format
SBML (L2V4)
Related Publication
  • Pharmacokinetics, lymph node uptake, and mechanistic PK model of near-infrared dye-labeled bevacizumab after IV and SC administration in mice.
  • Wu F, Tamhane M, Morris ME
  • The AAPS journal , 6/ 2012 , Volume 14 , Issue 2 , pages: 252-261 , PubMed ID: 22391791
  • Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, New York 14260, USA.
  • Our objective was to determine the pharmacokinetics, bioavailability and lymph node uptake of the monoclonal antibody bevacizumab, labeled with the near-infrared (IR) dye 800CW, after intravenous (IV) and subcutaneous (SC) administration in mice. Fluorescence imaging and enzyme-linked immunosorbent assay (ELISA) assays were developed and validated to measure the concentration of bevacizumab in plasma. The bevacizumab-IRDye conjugate remained predominantly intact in plasma and in lymph node homogenate samples over a 24-h period, as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and size exclusion chromatography. The plasma concentration vs. time plots obtained by fluorescence and ELISA measurements were similar; however, unlike ELISA, fluorescent imaging was only able to quantitate concentrations for 24 h after administration. At a low dose of 0.45 mg/kg, the plasma clearance of bevacizumab was 6.96 mL/h/kg after IV administration; this clearance is higher than that reported after higher doses. Half-lives of bevacizumab after SC and IV administration were 4.6 and 3.9 days, respectively. After SC administration, bevacizumab-IRDye800CW was present in the axillary lymph nodes that drain the SC site; lymph node uptake of bevacizumab-IRDye 800CW was negligible after IV administration. Bevacizumab exhibited complete bioavailability after SC administration. Using a compartmental pharmacokinetic model, the fraction absorbed through the lymphatics after SC administration was estimated to be about 1%. This is the first report evaluating the use of fluorescent imaging to determine the pharmacokinetics, lymphatic uptake, and bioavailability of a near-infrared dye-labeled antibody conjugate.
Contributors
Submitter of the first revision: Krishna Kumar Tiwari
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Krishna Kumar Tiwari

Metadata information

isDescribedBy (1 statement)
PubMed 22391791

hasProperty (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Non-curated
Modelling approach(es)
ordinary differential equation model
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Model files
Wu2017_v1.xml SBML L2V4 model file 21.76 KB Preview | Download

Additional files
Wu2017_v1.cps COPASI 4.27 (Build417) file 50.79 KB Preview | Download
Wu2017_v1.sedml SEDML file 4.28 KB Preview | Download

  • Model originally submitted by : Krishna Kumar Tiwari
  • Submitted: Mar 3, 2020 3:34:34 PM
  • Last Modified: Mar 5, 2020 12:00:17 PM
Revisions
  • Version: 4 public model Download this version
    • Submitted on: Mar 5, 2020 12:00:17 PM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Edited model metadata online.
  • Version: 2 public model Download this version
    • Submitted on: Mar 3, 2020 3:34:34 PM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Edited model metadata online.

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