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Related Experiment Videos

Bioanalytical strategies to support a discovery research programme

S A Rees1

  • 1Upjohn Laboratories--Europe, Crawley, West Sussex, UK.

Journal of Pharmaceutical and Biomedical Analysis
|June 1, 1996
PubMed
Summary

A novel three-level screening funnel strategy aids drug candidate selection by assessing preliminary metabolism and pharmacokinetics. This approach uses in-vitro and in-vivo methods, with evolving bioanalytical requirements for efficient drug discovery.

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Area of Science:

  • Pharmacology
  • Drug Discovery
  • Bioanalysis

Background:

  • Selecting viable drug candidates is crucial in discovery research.
  • Preliminary assessment of metabolism and pharmacokinetics informs candidate selection.
  • Efficient screening methods are needed for numerous chemical entities.

Purpose of the Study:

  • To develop and implement a multi-level screening strategy for early-stage drug candidate assessment.
  • To evaluate the utility of different bioanalytical methods across various pharmacokinetic studies.
  • To streamline the selection process for drug candidates.

Main Methods:

  • A three-level "screening funnel" approach combining in-vitro and in-vivo techniques.
  • Initial high-throughput in-vitro screening for metabolic stability using HPLC/UV.

Related Experiment Videos

  • In-vivo studies in rats for clearance and blood-brain barrier penetration assessment.
  • Rat oral/intravenous (PO/IV) bioavailability studies requiring sensitive assays.

    • Main Results:

    • High-performance liquid chromatography (HPLC)/UV assays with minimal sample workup sufficed for initial in-vitro screens.
    • More selective extraction methods were needed for subsequent in-vivo pharmacokinetic assessments.
    • The final bioavailability studies presented significant analytical challenges due to high sensitivity requirements.

    Conclusions:

    • A tiered screening strategy effectively facilitates drug candidate selection.
    • Bioanalytical method sensitivity requirements increase with each screening level.
    • The developed strategy optimizes the assessment of metabolism and pharmacokinetics in early drug discovery.