title: Prediction of drug clearance in children: an evaluation of the predictive performance of several models.
abstract: The objective of this study is to evaluate the predictive performance of several models to predict drug clearance in children ≤5 years of age. Six models (allometric model (data-dependent exponent), fixed exponent of 0.75 model, maturation model, body weight-dependent model, segmented allometric model, and age-dependent exponent model) were evaluated in this study. From the literature, the clearance values for six drugs from neonates to adults were obtained. External data were used to evaluate the predictive performance of these models in children ≤5 years of age. With the exception of a fixed exponent of 0.75, the mean predicted clearance in most of the age groups was within ≤50% prediction error. Individual clearance prediction was erratic by all models and cannot be used reliably to predict individual clearance. Maturation, body weight-dependent, and segmented allometric models to predict clearances of drugs in children ≤5 years of age are of limited practical value during drug development due to the lack of availability of data. Age-dependent exponent model can be used for the selection of first-in-children dose during drug development.
authors.affiliation: Division of Hematology, Office of Blood Review & Research (OBRR), Center for Biologic Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993-0002, USA, iftekhar.mahmood@fda.hhs.gov.
authors.forename: Iftekhar
authors.initials: I
authors.lastname: Mahmood
authors.forename: Carl-Michael
authors.initials: CM
authors.lastname: Staschen
authors.forename: Kosalaram
authors.initials: K
authors.lastname: Goteti
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D001835:Body Weight / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D003627:Data Interpretation, Statistical; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations