This service package has been designed to predict a dosage regime in man. It uses an FDA approved PBPK modelling system, GastroPlus™ to predict human oral bioavailability, clearance and distribution. Through its validated laboratory-based assays XenoGesis will generate the data to populate the model, ensuring accurate and robust inputs which are essential to produce an accurate modelled output.
Description of Service
Integration of pre-clinical in vitro and in vivo data to generate a PBPK model using GastroPlus™ and use of this model to predict human PK and efficacious dose.
- Caco-2 permeability
- Solubility in buffer and biorelevant media (thermodynamic – ideally PBS@ pH6.5, FeSSIF, FaSSIF and SGF)
- Blood:plasma ratio, hepatocyte CLint, and plasma protein binding (rat,dog and human)
- Rat and dog IV and PO PK including assessment of renal clearance
XenoGesis will provide a written report describing the in vitro-in vivo correlations of absorption, clearance and distribution in rat and dog using GastroPlus™. The report will evaluate whether an adjustment of the PBPK model is required to best match the observed data (IV and PO) in these species. After such an adjustment the final GastroPlus™ PBPK model detailing the behaviour of the client drug will be generated and used within human in vitro data to protect oral bioavailability, clearance and distribution in man. The model will be used to identify the predicted dose regime in man required to achieve a target unbound plasma concentration-time profile provided by the client (e.g. Cmin > concentration required for 90% target engagement).