In the body: Where, what and for how long?

For a medicine to work, a patient needs to take it in a form which results in the medicine:

  • Reaching where the parasite is hiding in the body
  • At a level which kills the parasite, but doesn’t harm the patient and
  • Then remain where the parasites live, at this level, for long enough to kill all the parasites

Studying this is called DMPK (Drug Metabolism and PharmacoKinetics). DMPK, as a discipline, works very closely with medicinal chemistry. It ensures that a compound has the appropriate properties to progress through development with a high chance of success.  In DMPK we use a host of in vitro, in vivo and computational simulation and prediction technologies. In early drug discovery, these aid the production of drug-like compounds. We can prioritise compounds that show the right balance of properties.  It is not just about finding a highly potent molecule against the parasite.  Often a less potent compound against the parasite might be the best choice if it has superior DMPK properties.

WCAIR is supporting DMPK through development of

  • In vitro pharmacokinetic/pharmacodynamic (PKPD) models
  • Computer modelling
  • Animal disease model refinement
  • Enhanced (Bio)Analytical capability

Read more about each of these activities by clicking on links below.

 At WCAIR we support the 3R’s initiative: Reduction, Refinement and / or Replacement of animals used to test compounds. The Centre is therefore investigating and refining new methodologies. These will allow us to know if a compound is likely to have good DMPK properties through cell based experiments and computer modelling. We then only test the most promising compounds in animal models. Only by observing the compound in an animal model allows us to make predictions about what will really happen when the compound is given to a patient. Investing in new approaches will allow us to use fewer animals. It will also give better information to predict how the DMPK properties of the compound translate from animal models to patients.

In vitro dynamic PKPD studies

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Computer modelling

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Chagas disease mouse model of infection

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Enhanced (Bio)Analytical capability

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