Toxicology

Acute Toxicity

How much compound can be given?

 preclinical toxicology testingFor compounds that have shown activity in in vitro testing, it is important to establish a toxicity profile before moving on to costly efficacy studies. To accomplish this, Pharma Models offers very cost effective model of acute toxicity, in which the compound is given to mice on a dose escalation protocol, and the mice are observed for 24 hours. This test is tailored to meet the individual clients needs based on strain of mouse and route of administration, which are usually selected based on the eventual efficacy model to be targeted with each compound.

This model is generally used to

  • (a) determine which of a series of compounds has an unfavorable toxicity profile (if any), and
  • (b) to select doses for a longer determination of tolerability over multiple doses, which would be the final evaluation prior to moving into an efficacy study, in an animal model of human disease.

Multiple-Dose Tolerability

What is a reasonable repeat dose?

As a novel compound is moved into animal testing, a critical factor is determining how much compound can be given, how frequently this dose can be given, and by which routes of administration the compound can be given. To accomplish this, it is often cost-effective to conduct a study of tolerability in which the compound is given once daily or once every other day at one or more doses with the animal’s reaction to the compound monitored, usually by monitoring weight loss, but also through the evaluation of animal behavior.

In this way, the potential toxicity of the compound in an animal model of human disease can be obtained, without the risk and expense of putting the compound directly into the animal model study. In this way, the chance of unexpected failures can be minimized.

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