High-throughput prediction of fraction absorbed and bioavailability in silico

Conference: ACS
Software: GastroPlus®
Division: Simulations Plus


• Late-stage attrition due to obviously bad physicochemical properties has been reduced by application of rules-of thumb
like Lipinski’s Rule of Five.
• Failure due to lack of efficacy remains a major issue. This can be due to a poor choice of target, but can also reflect poor pharmacokinetics (PK).
• Combinations of physicochemical properties may be problematic even when each individual property seems
• This can make it hard to know which property to modify next, e.g., decreasing hydrophobicity to try to address
problems with solubility and metabolism is likely to decrease absorption as well. Is there a way to explore the pharmacokinetic landscape before enough compound has been synthesized to assess its PK behavior in vivo?

American Chemical Society National Meeting & Expo 2018, March 18-22, 2018, New Orleans, Louisiana

By Robert D. Clark, Pankaj Daga and Robert Fraczkiewicz