Use of PACT-F
Preclinical And Clinical Trials Knowledge Base on Bioavailability
PACT-F is the fundamental knowledge base on bioavailability which allows to
For the first time, it is now possible to answer fundamental questions of life between humans and animals:
PACT-F is a structure-based knowledge base. This enables scientists to build relationships between structures and bioavailability (QSBR), such as which molecular patterns increase or decrease the bioavailability of a drug, either generally in all organisms or only in some specific species.
PACT-F is used to identify functional groups or molecular patterns which commonly lead to a low oral bioavailability in some species, like rats, but which don’t affect human oral bioavailability. This is due to genetic species differences or different metabolic pathways, making animal trials less reliable to project human oral bioavailability. In these cases, a bioavailability trial in this species will mislead the candidate selection process in drug development.
PACT-F has been used to estimate inter-subject variability of oral bioavailability in humans, results are here.
Small changes within the chemical structure can modify the bioavailability of an investigational drug dramatically. PACT-F can be used to identify and quantify the effects of substitution of functional groups.
Based on the large amount of available structures and bioavailability values in PACT-F, computational models such as neural networks or decision trees can be evolved which will guide the future optimisation of investigational compounds and the selection of drug candidates for clinical trials.
The expert system IMPACT-F which calculates oral bioavailability of novel drug candidates is based of the knowledge of PACT-F.