GastroPlus™

PBPK modeling software – from discovery through
development…

Choose a Module:

Biologics

What is the Biologics Module?

Starting in GastroPlus 9.0, we are pleased to offer PBPK models for large molecules (biologics). The Biologics Module simulates the systemic absorption and pharmacokinetics of biologics – for both monoclonal antibodies (mAb) and now antibody-drug conjugates (ADCs). In the current implementation, both mAbs and ADCs administered as an intravenous bolus dose, intravenous infusion, or subcutaneous (SQ) injection can be modeled.

As with other GastroPlus modules, there is no equation or code writing required. A schematic diagram of how the different organs are connected to one another is shown below. All major organs are connected in an anatomical fashion with plasma flow represented by blue solid arrows and lymph flow by red dashed arrows.

The lymph node collects the lymphatic drainage from organs and lymph fluid is returned to the systemic circulation. Each organ in the PBPK model is divided into three major compartments representing the vascular, endosomal, and interstitial spaces, as shown below.

Some of the key processes accounted for in the GastroPlus models include:

  • Convective transport and fluid phase endocytosis describing uptake of antibody into the tissue
  • mAb-FcRn (neonatal FC receptor) binding & recycling
  • 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) or subcutaneous (SQ) injection
  • Complete default physiology parameters for humans – flexibility to create custom species models