Iftekhar Mahmood1. 1. Division of Hematology, Office of Blood Review and Research, Center for Biologic Evaluation and Research, Food and Drug Administration, Rockville, MD, USA. iftekhar.mahmood@fda.hhs.gov
Abstract
BACKGROUND: Sometimes it might not be possible to conduct a pharmacokinetic (PK) study in neonates and infants. Under these circumstances, one would like to predict PK parameters in this age group. Because drug clearance is the most important PK parameter, the objective of this study was to describe an allometric method to predict drug clearance in children ≤3 months. METHODS: In total, 43 drugs (107 observations) were randomly selected for this study. The age of the children ranged from 0 to 1 year. Children were divided into two groups: ≤3 months and ≥3 months to 1 year. Drug clearance (CL) in children was predicted using the following equation: CL in the child=adult CL×(weight of the child/70)(0.75 or 1.0 or 1.2). RESULTS: The results of the study indicated that the exponent 1.2 performs better in the prediction of drug clearance than exponent 1.0 or 0.75 for children ≤3 months. By contrast, exponent 1.0 provided better prediction for children ≥3 months to 1 year than exponent 1.2. Exponent 0.75 provided the worst results leading to substantial prediction error in children 0-1 year (in many instances more than 1000% prediction error). CONCLUSIONS: Overall, it appears that exponent 1.2 is the best method out of three methods for reasonably accurate prediction of drug clearance in children ≤3 months old. However, exponent 1.2 will underpredict drug clearance in children older than 3 months. The suggested approach could be used to support the choice of the initial dose in clinical trials for children ≤3 months old.
BACKGROUND: Sometimes it might not be possible to conduct a pharmacokinetic (PK) study in neonates and infants. Under these circumstances, one would like to predict PK parameters in this age group. Because drug clearance is the most important PK parameter, the objective of this study was to describe an allometric method to predict drug clearance in children ≤3 months. METHODS: In total, 43 drugs (107 observations) were randomly selected for this study. The age of the children ranged from 0 to 1 year. Children were divided into two groups: ≤3 months and ≥3 months to 1 year. Drug clearance (CL) in children was predicted using the following equation: CL in the child=adult CL×(weight of the child/70)(0.75 or 1.0 or 1.2). RESULTS: The results of the study indicated that the exponent 1.2 performs better in the prediction of drug clearance than exponent 1.0 or 0.75 for children ≤3 months. By contrast, exponent 1.0 provided better prediction for children ≥3 months to 1 year than exponent 1.2. Exponent 0.75 provided the worst results leading to substantial prediction error in children 0-1 year (in many instances more than 1000% prediction error). CONCLUSIONS: Overall, it appears that exponent 1.2 is the best method out of three methods for reasonably accurate prediction of drug clearance in children ≤3 months old. However, exponent 1.2 will underpredict drug clearance in children older than 3 months. The suggested approach could be used to support the choice of the initial dose in clinical trials for children ≤3 months old.
Authors: Christoph P Hornik; Daniel Gonzalez; Julie Dumond; Huali Wu; Eric M Graham; Kevin D Hill; Michael Cohen-Wolkowiez Journal: CPT Pharmacometrics Syst Pharmacol Date: 2019-10-23