The allometric exponent for scaling clearance varies with age: a study on seven propofol datasets ranging from preterm neonates to adults

Authors

  • Chenguang Wang,

    1. Division of Pharmacology, LACDR, Leiden University, Leiden, the Netherlands
    2. Intensive Care and Department of Paediatric Intensive Care, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands
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  • Karel Allegaert,

    1. Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium
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  • Mariska Y. M. Peeters,

    1. Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, the Netherlands
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  • Dick Tibboel,

    1. Intensive Care and Department of Paediatric Intensive Care, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands
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  • Meindert Danhof,

    1. Division of Pharmacology, LACDR, Leiden University, Leiden, the Netherlands
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  • Catherijne A. J. Knibbe

    Corresponding author
    1. Division of Pharmacology, LACDR, Leiden University, Leiden, the Netherlands
    2. Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, the Netherlands
    • Correspondence

      Prof Dr Catherijne A. J. Knibbe PharmD, PhD, Department of Clinical Pharmacy, St Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein, the Netherlands.

      Tel.: +313 0609 2612

      Fax: +313 0609 3080

      E-mail: c.knibbe@antoniusziekenhuis.nl

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Abstract

Aim

For scaling clearance between adults and children, allometric scaling with a fixed exponent of 0.75 is often applied. In this analysis, we performed a systematic study on the allometric exponent for scaling propofol clearance between two subpopulations selected from neonates, infants, toddlers, children, adolescents and adults.

Methods

Seven propofol studies were included in the analysis (neonates, infants, toddlers, children, adolescents, adults1 and adults2). In a systematic manner, two out of the six study populations were selected resulting in 15 combined datasets. In addition, the data of the seven studies were regrouped into five age groups (FDA Guidance 1998), from which four combined datasets were prepared consisting of one paediatric age group and the adult group. In each of these 19 combined datasets, the allometric scaling exponent for clearance was estimated using population pharmacokinetic modelling (nonmem 7.2).

Results

The allometric exponent for propofol clearance varied between 1.11 and 2.01 in cases where the neonate dataset was included. When two paediatric datasets were analyzed, the exponent varied between 0.2 and 2.01, while it varied between 0.56 and 0.81 when the adult population and a paediatric dataset except for neonates were selected. Scaling from adults to adolescents, children, infants and neonates resulted in exponents of 0.74, 0.70, 0.60 and 1.11 respectively.

Conclusions

For scaling clearance, ¾ allometric scaling may be of value for scaling between adults and adolescents or children, while it can neither be used for neonates nor for two paediatric populations. For scaling to neonates an exponent between 1 and 2 was identified.

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