Prediction of drug clearance in children: a review of different methodologies

Abstract

Introduction: Children are not small adults because the differences between adults and children are not simply due to body weight, but also due to physiological and biochemical differences. Hence, dosing in children should not be a ‘small adult dose’. During pediatric drug development, selection of a suitable dose for the first-in-children clinical study (Pharmacokinetic [PK], safety and efficacy) is of utmost importance. Considering the importance of clearance in dose selection, a lot of approaches have been suggested for the prediction of drug clearance in children. This review examines many proposed methods for the prediction of drug clearance in the pediatric population and highlights the application and limitations of these proposed methods.

Areas covered: In this review, different methods for the prediction of drug clearance in the pediatric population are discussed. These methods include allometric models, population-based pharmacometric models and physiologically based PK models.

Expert opinion: All models discussed here have uncertainties in their predictive power and should be only used as exploratory tools during pediatric drug development. Allometric models, if used with knowledge and understanding, is a powerful tool for the prediction of drug clearance in pediatric population.

Keywords:

• allometric models
• children
• drug clearance
• physiological models
• population-based pharmacometric models

Acknowledgement

The author thanks Dr. Gilbert Burckart, Associate Director of Pediatrics, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration for reviewing this manuscript and providing helpful suggestions.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties. The views expressed in this article are those of the author and do not reflect the official policy of the FDA. No official support or endorsement by the FDA is intended or should be inferred.

Notes

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