02. Processes considered
PBPK models for (mAb) and (ADCs)
  • PBPK models for monoclonal antibodies (mAb) - processes considered:
    • Convective transport and fluid phase endocytosis describing uptake of antibody into the tissue
    • mAb-FcRn (neonatal FC receptor) binding & recycling – including pH-dependent binding kinetics
    • Target mediated elimination in the interstitial space to include the influence of specific antigen-mAb interactions on mAb disposition
    • Within the endosomal space, the competition for binding to FcRn between endogenous IgG and the therapeutic mAb
    • mAb administration by either intravenous (IV), subcutaneous (SQ), or intramuscular injections
    • Default physiology parameters for humans & animals – with the flexibility to create custom models

    A detailed flowchart diagram representing the human body's blood circulation system—including organs like the lungs, liver, spleen, heart, and kidneys—features annotations, arrows, numerical values indicating blood flow dynamics and physiological functions with insights into the pharmacokinetics of biologics using Simulations Plus Inc.'s GastroPlus

    A complex scientific diagram depicts the pharmacokinetics of biologics, leveraging Simulations Plus, Inc's ADMET Predictor for IgG interactions in vascular (red), endosomal (purple), and interstitial (orange) spaces, and using GastroPlus to model chemical reactions and exchange processes with various equations and variables.

  • PBPK models for antibody-drug conjugates (ADCs) - processes considered:
    • Distribution and elimination processes of multiple ADC species with different DAR (drug-to-antibody ratio)
    • Clearance defined through nonspecific mechanisms
    • Binding to target receptor, internalize, and be cleared in the cell lysosome
    • Release and clearance of the toxin molecule
      • Toxins can fall off antibody due to deconjugation
      • Released toxins can be cleared through metabolism or renally
    • Two types of deconjugation models included:
      • Series of transit processes to describe deconjugation from high to low DARs
      • Average DAR used to describe deconjugation step
03. Resources
Biologics Resources