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Assessing the utility of an anti-malarial pharmacokinetic-pharmacodynamic model for aiding drug clinical development

Sophie Zaloumis*, Andrew Humberstone, Susan A Charman, Ric N Price, Joerg Moehrle, Javier Gamo-Benito, James McCaw, Kris M Jamsen, Katherine Smith and Julie A Simpson

Malaria Journal 2012, 11:303  doi:10.1186/1475-2875-11-303

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A pointer to previous work on this topic.

Ian Hastings   (2012-11-26 15:02)  Division of Tropical Medicine, Liverpool School of Tropical Medicine

Readers should be aware that we published a very similar PK/PD methodology and analysis of antimalarial drugs last year in AAC that is not cited or discussed in this manuscript i.e.

Winter, K. and I. M. Hastings (2011). "Development, evaluation and application of an in silico model for antimalarial drug treatment and failure." Antimicrobial Agents and Chemotherapy 55: 3380-3392.

In summary, we reported that our models were very robust and generated model outputs that were highly consistent with clinical data. We have been further refining and applying these models (unpublished data) and continue to find excellent matches with field and clinical data.

[One notable difference is that we implemented our methodology in half- and one-day timesteps rather than the one-hour timesteps used by Zaloumis et al. This was to avoid having to incorporate, and further calibrate, the stage-specific killing of drugs: our reasoning was that artemisinins have a short half-life but broad stage-specific killing ranges while the partner drugs have narrower stage specificity but long half-lives so will be present at high concentrations throughout the malaria cell cycles subsequent to drug administration. This choice reflected a trade off between biological realism and the desire to avoid over-elaborating our PK/PD model.]

Ian Hastings and Katherine Winter

Competing interests

None declared

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