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


METHODS
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.


CONCLUSIONS
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.
Center 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.
Iftekhar
I
Mahmood
D000328:Adult; D000367:Age Factors; D000818:Animals; D002648:Child; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008954:Models, Biological; D010599:Pharmacokinetics
allometric models; children; drug clearance; physiological models; population-based pharmacometric models