The road map to oral bioavailability: an industrial perspective

Abstract

Optimisation of oral bioavailability is a continuing challenge for the pharmaceutical and biotechnology industries. The number of potential drug candidates requiring invivo evaluation has significantly increased with the advent of combinatorial chemistry. In addition, drug discovery programmes are increasingly forced into more lipophilic and lower solubility chemical space. To aid in the use of invitro and insilico tools as well as reduce the number of invivo studies required, a team-based discussion tool is proposed that provides a road map to guide the selection of profiling assays that should be considered when optimising oral bioavailability. This road map divides the factors that contribute to poor oral bioavailability into two interrelated categories: absorption and metabolism. This road map provides an interface for cross discipline discussions and a systematic approach to the experimentation that drives the drug discovery process towards a common goal acceptable oral bioavailability using minimal resources in an acceptable time frame.

Keywords::

• absorption
• ADME optimisation
• bioavailability
• distribution
• drug discovery
• elimination
• metabolism
• pharmacokinetics
• solubility

Acknowledgements

The authors wish to thank M Mollan and J Brodfuehrer for their helpful review of this manuscript.

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