Automation and High Throughput Technologies

Podium

Using a novel microfluidics device to replicate drug PK profiles in vitro to improve in vivo translation of drug actions

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  Clay Scott, PhD

  Assoc Director, Oncology Safety Sciences
  AstraZeneca Pharmaceuticals

Drug effects are traditionally quantified in cell-based assays by testing drugs under static conditions and calculating the drug concentration that modulates the response by 50% (e.g. EC50).  In contrast, drug administration in vivo results in dynamic changes in drug concentration due to absorption, biodistribution and elimination.  Thus, a more quantitative translational assessment of drug-induced effects can be achieved when in vitro data is coupled to pharmacokinetic/pharmacodynamic (PK/PD) models, which allow translation of time-course and magnitude across biological systems, accounting for differences between in vitro and in vivo physiology.  This presentation will describe the development and use of a microfluidics system to replicate in vivo PK profiles with cell-based assays to enable improved in vivo translation of drug actions.  The system can be used to compare different PK profiles and dose scheduling paradigms to optimize drug-induced biological responses.  The instrument can be used to quantify a desired biological response (efficacy) as well as an undesired side effect to establish an in vitro therapeutic index.  This system has the potential to minimize animal studies for both efficacy and safety evaluation and effectively guide clinical use of candidate drugs.