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J Clin Pharmacol. 2015 Jul;55(7):739-47. doi: 10.1002/jcph.488. Epub 2015 May 25.

Prediction of drug clearance in children.

Foissac F1,2,3, Bouazza N1,2,3, Valade E1,2,3, De Sousa Mendes M1,2,3, Fauchet F1,2,3, Benaboud S1,2,3,4, Hirt D1,2,3,4, Tréluyer JM1,2,3,4, Urien S1,2,3.

Author information

1
EA 08, Université Paris Descartes, Sorbonne Paris Cité, France.
2
Unité de Recherche Clinique, Assistance Publique Hôpitaux de Paris (APHP), Hôpital Tarnier, Paris, France.
3
CIC-1419 Inserm, Cochin-Necker, Paris, France.
4
Laboratoire de Pharmacologie, Hôpital Cochin, APHP, Paris, France.

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.

KEYWORDS:

allometric scaling; clearance; elimination; maturation; pediatric

PMID:
25721251
DOI:
10.1002/jcph.488
[Indexed for MEDLINE]

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