Oral bioavailability (F%) is the fraction of an oral administered drug that reaches systemic circulation.
After intravenous administration, a drug is directly and fully available in the bloodstream and can be distributed via systemic circulation to the point where a pharmacological effect takes place. If a drug is administered orally, it has to cross further barriers to reach the systemic circulation, which can significantly reduce the final extent of a drug in the bloodstream.
Oral bioavailability is one of the most important properties in drug design and development. A high oral bioavailability reduces the amount of an administered drug necessary to achieve a desired pharmacological effect and therefore could reduce the risk of side-effects and toxicity. A poor oral bioavailability can result in low efficacy and higher inter-individual variability and therefore can lead to unpredictable response to a drug.
Low oral bioavailability in clinical trials is a major reason for drug candidates failing to reach the market. Therefore, several strategies have been developed to estimate human oral bioavailability of novel drug candidates.
A large number of animal trials are conducted every year to estimate human oral bioavailability. Up to now it was uncertain, if animal trials are meaningful and reliable to estimate human response, since a comprehensive bioavailability database, combining results from animal trials and human clinical trials was missing.
The development of the Preclinical and Clinical Trials Knowledge Base (PACT-F) now allows to analyse and quantify differences in oral bioavailability between humans and animals based on a large number of drugs. Research findings are presented here.
Lead Optimization (LO):
Structural modifications of initial hits can yield to optimised leads which can proceed to drug candidates.
Quantitative structure activity relationship (QSAR):
Chemical structures are set in relation to their biological activity.
Absorption & Distribution & Metabolism & Excretion (ADME):
Oral bioavailability combines both absorption and metabolism.
Quantitative structure property relationship (QSPR):
Oral bioavailability is a key property of leads or drug candidates.