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Prediction of Antimalarial Drug Clearance in Children: A Comparison of Three Different Interspecies Scaling Methods

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Abstract

Background and objective

Allometric scaling is extensively used for the prediction of pharmacokinetic parameters from animals to humans and is often used for the selection of first-in-human dose. Allometric scaling can also be used to predict a pharmacokinetic parameter in children from adult data including animal species such as rat and dog. The current study was undertaken to evaluate if the clearances of antimalarial drugs in children with malaria can be predicted allometrically (interspecies scaling) from adult rat, dog, and human adult (healthy as well patients with malaria) clearance values.

Methods

Three methods [simple allometry, maximum lifespan potential (MLP), and MLP with an empirical correction factor] using clearance values from adult rat, dog, and adult humans with and without malaria were used for the prediction of antimalarial drug clearance in children with malaria.

Results

The results of this study indicated that the simple allometry would systematically over-predict antimalarial drug clearance in children with malaria whereas the application of MLP would under-predict the clearances of these drugs in children. Therefore, an empirical correction factor was introduced to MLP which substantially improved the antimalarial drug clearances in children.

Conclusions

Overall, the results of the study indicated that interspecies scaling using adult rat, dog, and human clearance values of antimalarial drugs could possibly be used to predict drug clearance in children with malaria of different age groups and may be useful during pediatric drug development of antimalarial drugs.

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Acknowledgments

The authors would like to acknowledge the assistance of Dr. Gilbert Burckart in the preparation and editing of this manuscript. This work was not supported by any private or government fund.

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Authors and Affiliations

  1. Division of Hematology Clinical Review, Office of Blood Review and Research (OBRR), Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, 20993-0002, USA

    Iftekhar Mahmood

  2. School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA, 90089, USA

    Anna Cheng & Edward Brauer

  3. Office of the Commissioner, US Food and Drug Administration, Silver Spring, MD, 20993-0002, USA

    Rita Humeniuk

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  1. Iftekhar Mahmood
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Mahmood, I., Cheng, A., Brauer, E. et al. Prediction of Antimalarial Drug Clearance in Children: A Comparison of Three Different Interspecies Scaling Methods. Eur J Drug Metab Pharmacokinet 41, 767–775 (2016). https://doi.org/10.1007/s13318-015-0305-2

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