Cyprotex have authored a peer reviewed article in the Journal of Pharmaceutical Sciences (Thomas et al., 2008 J Pharmaceut Sci 97 (10), 4557-4574). The title of the article is 'Simulation Modelling of Human Intestinal Absorption using Caco-2 Permeability and Kinetic Solubility Data for Early Drug Discovery.' The article describes the use of Cloe® Screen Caco-2 permeability and Cloe® Screen Solubility data in the prediction of in vivo human intestinal absorption using our Cloe® Predict physiologically based pharmacokinetic (PBPK) modelling expertise. The model addresses issues such as dose dependency and dose limitation and improves the prediction of human intestinal absorption over using Caco-2 data alone.
Caco-2 permeability is a popular surrogate for the permeation of a compound across the gastrointestinal tract. However, Caco-2 alone does not take into consideration confounding factors such as solubility and dissolution in the gastrointestinal tract fluids. By incorporating both Caco-2 and solubility data in the estimation of human intestinal absorption it is possible to achieve superior prediction power over in vitro permeability data alone. The model features novel simulation of time-dependent fluid volumes as a consequence of secretions into and absorption from the upper parts of the gastrointestinal tract.
Access to the model is now available under our Cloe® Predict portfolio of offerings. Cloe® Predict covers a number of proprietary predictive technologies such as Cloe® PK which uses ADME input data to predict the whole body pharmacokinetics and the Cyprotex Discovery Bus which includes a novel auto QSAR system. All technologies under Cloe® Predict are developed and are owned by Cyprotex Discovery Ltd.
The overall drive in the Pharmaceutical Industry is to improve efficiency and reduce operating costs. Implementation of in silico techniques is one route to achieving this goal and predictive methods are now becoming widely accepted within the industry. Smarter use of experimental data and the incorporation of PBPK modelling techniques will enable a greater understanding of the relationship between in vitro ADME data and in vivo pharmacokinetics.
Dr Anthony Baxter, Cyprotex's Chief Executive Officer, comments. "Cyprotex have built a unique facility where we can offer rapid, high quality screening coupled with predictive modelling expertise. This combination sets us apart from our competitors and allows us to provide added-value to the screening data by offering an insight into how the in vitro data relates to the in vivo human situation in a discovery setting."
For further information:
Helen Gill PhD, Product Development Manager
Tel: +44 (0)1625 505 100