title: Prediction of Drug Clearance in Premature and Mature Neonates, Infants, and Children ≤2 Years of Age: A Comparison of the Predictive Performance of 4 Allometric Models.
abstract: The objective of this study was to evaluate the predictive performance of 4 allometric models to predict clearance in pediatric ages ranging from premature neonates to children ≤2 years of age. Four allometric models were used to predict clearances of 28 drugs in children from preterm neonates to 2 years of age (n = 564). The 4 models are (1) basal metabolic rate-dependent model; (2) age-dependent exponent model; (3) an allometric model based on kidney and liver weights as well as kidney and liver blood flow; and (4) an allometric model based on a fixed exponent of 0.75. The predictive performance of these models was evaluated by comparing the predicted clearance of the studied drugs with the observed clearance in an individual child. The results of the study indicated that the 3 new proposed models predicted the mean clearance of the drugs with reasonable accuracy (≤50% prediction error). On the other hand, the exponent of 0.75 produced substantial prediction error. Predicted individual clearance values were ≥50% in approximately 30% of the children by the proposed 3 methods and 73% by exponent 0.75. The 3 new proposed allometric models can predict mean clearances of drugs in children from premature neonates to ≤2 years of age with reasonable accuracy and are of practical value during pediatric drug development.
authors.affiliation: Division of Hematology Clinical Review, Office of Blood Review & Research (OBRR), Center for Biologic Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Iftekhar
authors.initials: I
authors.lastname: Mahmood
mesh_terms: D000367:Age Factors; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism*; D011237:Predictive Value of Tests
chemical_list: D004364:Pharmaceutical Preparations
keywords: allometry; clearance; exponents; pediatrics