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Prediction of drug clearance in children: a review of different methodologies
1Center for Biologic Evaluation and Research, Office of Blood Review and Research (OBRR), Division of Hematology, US Food and Drug Administration , Silver Spring, MD , USA +1 301 402 8418 ; Iftekhar.mahmood@fda.hhs.gov.
Insights
Predicting drug clearance in children is crucial for safe and effective pediatric drug development. This review evaluates methods like allometric, pharmacometric, and physiologically based models, noting their limitations and utility as exploratory tools.
Area of Science:
- Pharmacology
- Pediatric Drug Development
Background:
- Pediatric drug dosing requires specialized approaches due to physiological and biochemical differences between children and adults.
- Accurate prediction of drug clearance is vital for selecting appropriate doses in early-stage pediatric clinical studies.
Purpose of the Study:
- To review and analyze various methods for predicting drug clearance in the pediatric population.
- To highlight the applications and limitations of different predictive models in pediatric drug development.
Main Methods:
- Discussion of allometric models for predicting pediatric drug clearance.
- Examination of population-based pharmacometric models.
- Review of physiologically based pharmacokinetic (PK) models.
Main Results:
- Various models exist for predicting pediatric drug clearance, each with unique strengths and weaknesses.
- All discussed models possess inherent uncertainties and should be employed as exploratory tools.
Conclusions:
- Allometric models can be powerful for predicting pediatric drug clearance when applied with expertise.
- Models for predicting pediatric drug clearance are valuable but require careful interpretation in drug development.
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.
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