title: Prediction of drug clearance in children.
abstract: The pediatric population is often exposed to drugs without sufficient knowledge about pharmacokinetics. The prediction of accurate clearance values in children, especially in neonates and infants, will improve the rational in dosing decisions. Drug clearances from birth to adulthood were compiled after a systematic review of pharmacokinetic reports. The analysis was performed using NONMEM. Clearance predictions were then evaluated by external validation. Prediction errors were also compared with those obtained from weight-based allometric scaling and physiologically based clearance (PBCL) models. For the analysis, 17 and 15 drugs were used for model building and external validation, respectively. A model based on the adult drug clearance value and taking into account both weight and age was retained. Age-related maturation of clearance reached 90% of the adult value within 1.5 years of life. For children less than 2 years old, allometric scaling alone systematically overestimated clearances. Accounting for age improved the clearance prediction in the 6 months-2 years age group (prediction error < 25%). Predictions obtained from the PBCL approach were close to our results. This analysis established a single equation using the adult clearance value as well as individual age and weight to predict drug clearance in children older than 6 months.
authors.affiliation: EA 08, Université Paris Descartes, Sorbonne Paris Cité, France.|Unité de Recherche Clinique, Assistance Publique Hôpitaux de Paris (APHP), Hôpital Tarnier, Paris, France.|CIC-1419 Inserm, Cochin-Necker, Paris, France.
authors.forename: Frantz
authors.initials: F
authors.lastname: Foissac
authors.affiliation: EA 08, Université Paris Descartes, Sorbonne Paris Cité, France.|Unité de Recherche Clinique, Assistance Publique Hôpitaux de Paris (APHP), Hôpital Tarnier, Paris, France.|CIC-1419 Inserm, Cochin-Necker, Paris, France.
authors.forename: Naïm
authors.initials: N
authors.lastname: Bouazza
authors.affiliation: EA 08, Université Paris Descartes, Sorbonne Paris Cité, France.|Unité de Recherche Clinique, Assistance Publique Hôpitaux de Paris (APHP), Hôpital Tarnier, Paris, France.|CIC-1419 Inserm, Cochin-Necker, Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Valade
authors.affiliation: EA 08, Université Paris Descartes, Sorbonne Paris Cité, France.|Unité de Recherche Clinique, Assistance Publique Hôpitaux de Paris (APHP), Hôpital Tarnier, Paris, France.|CIC-1419 Inserm, Cochin-Necker, Paris, France.
authors.forename: Mailys
authors.initials: M
authors.lastname: De Sousa Mendes
authors.affiliation: EA 08, Université Paris Descartes, Sorbonne Paris Cité, France.|Unité de Recherche Clinique, Assistance Publique Hôpitaux de Paris (APHP), Hôpital Tarnier, Paris, France.|CIC-1419 Inserm, Cochin-Necker, Paris, France.
authors.forename: Floris
authors.initials: F
authors.lastname: Fauchet
authors.affiliation: EA 08, Université Paris Descartes, Sorbonne Paris Cité, France.|Unité de Recherche Clinique, Assistance Publique Hôpitaux de Paris (APHP), Hôpital Tarnier, Paris, France.|CIC-1419 Inserm, Cochin-Necker, Paris, France.|Laboratoire de Pharmacologie, Hôpital Cochin, APHP, Paris, France.
authors.forename: Sihem
authors.initials: S
authors.lastname: Benaboud
authors.affiliation: EA 08, Université Paris Descartes, Sorbonne Paris Cité, France.|Unité de Recherche Clinique, Assistance Publique Hôpitaux de Paris (APHP), Hôpital Tarnier, Paris, France.|CIC-1419 Inserm, Cochin-Necker, Paris, France.|Laboratoire de Pharmacologie, Hôpital Cochin, APHP, Paris, France.
authors.forename: Déborah
authors.initials: D
authors.lastname: Hirt
authors.affiliation: EA 08, Université Paris Descartes, Sorbonne Paris Cité, France.|Unité de Recherche Clinique, Assistance Publique Hôpitaux de Paris (APHP), Hôpital Tarnier, Paris, France.|CIC-1419 Inserm, Cochin-Necker, Paris, France.|Laboratoire de Pharmacologie, Hôpital Cochin, APHP, Paris, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Tréluyer
authors.affiliation: EA 08, Université Paris Descartes, Sorbonne Paris Cité, France.|Unité de Recherche Clinique, Assistance Publique Hôpitaux de Paris (APHP), Hôpital Tarnier, Paris, France.|CIC-1419 Inserm, Cochin-Necker, Paris, France.
authors.forename: Saïk
authors.initials: S
authors.lastname: Urien
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008954:Models, Biological; D017711:Nonlinear Dynamics; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics
chemical_list: D004364:Pharmaceutical Preparations
keywords: allometric scaling; clearance; elimination; maturation; pediatric