• Iftekhar Mahmood and Million A Tegenge.
• Office of Tissue & Advanced Therapies, Center for Biologics Evaluation and Research, Food & Drug Administration, Silver Spring, MD, USA.
• J Clin Pharmacol. 2019 Feb 1; 59 (2): 189-197.

AbstractThe objective of this study was to compare the predictive performance of an allometric model with that of a physiologically based pharmacokinetic (PBPK) model to predict clearance or area under the concentration-time curve (AUC) of drugs in subjects from neonates to adolescents. From the literature, 10 studies were identified in which clearance or AUC of drugs from neonates to adolescents was predicted by PBPK models. In these published studies, drugs were given to children either by intravenous or oral route. The allometric model was an age-dependent exponent (ADE) model for the prediction of clearance across the age groups. The predicted clearance or AUC values from the PBPK and ADE models were compared with the experimental values. The acceptable prediction error was the percentage of subjects within an 0.5- to 2-fold or 0.5- to 1.5-fold prediction error. There were 73 drugs with a total of 372 observations. From PBPK and allometric models, 91.1% and 90.6% of observations were within 0.5- to 2-fold prediction error, respectively. For children ≤2 years old (n = 130), PBPK and allometric models had 89% and 87% of observations within the 0.5- to 2-fold prediction error, respectively. This study indicates that the predictive power of PBPK and allometric models was essentially similar for the prediction of clearance or AUC in pediatric subjects ranging from neonates to adolescents.© 2018, The American College of Clinical Pharmacology.

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