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Emetic liability testing in ferrets.

Mark A Osinski1, Terese R Seifert, Thomas K Shaughnessy

  • 1Abbott Laboratories, Abbott Park, Illinois, USA.

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Summary
This summary is machine-generated.

Early identification of a drug candidate's potential to cause vomiting or nausea is crucial. A simple ferret model can predict these gastrointestinal side effects, aiding drug development success.

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Area of Science:

  • Pharmacology
  • Drug Discovery
  • Toxicology

Background:

  • Drug registration requires evidence of efficacy and safety, but patient tolerability is key for acceptance.
  • Gastrointestinal adverse events frequently limit the maximum tolerated dose (MTD) in early clinical trials.
  • Failure to achieve efficacious plasma concentrations at the MTD due to tolerability issues can lead to project failure.

Purpose of the Study:

  • To describe a simple method for evaluating the emetic and nauseogenic potential of drug candidates.
  • To highlight the importance of early identification of gastrointestinal liability in drug discovery.

Main Methods:

  • Utilizing ferrets, a species known to vomit in response to various stimuli, as a model organism.
  • Administering candidate drugs to ferrets to assess emetic and nauseogenic responses.

Main Results:

  • The described method allows for the evaluation of a compound's potential to induce vomiting and nausea.
  • This assessment can be performed early in the drug discovery process.

Conclusions:

  • Ferrets provide a viable model for predicting drug-induced emesis and nausea.
  • Early assessment of emetic/nauseogenic liability in ferrets can significantly impact the success of drug discovery projects.