title: The allometric exponent for scaling clearance varies with age: a study on seven propofol datasets ranging from preterm neonates to adults.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Pharmacology, LACDR, Leiden University, Leiden, the Netherlands; Intensive Care and Department of Paediatric Intensive Care, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Wang
authors.forename: Karel
authors.initials: K
authors.lastname: Allegaert
authors.forename: Mariska Y M
authors.initials: MY
authors.lastname: Peeters
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: Meindert
authors.initials: M
authors.lastname: Danhof
authors.forename: Catherijne A J
authors.initials: CA
authors.lastname: Knibbe
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D066264:Datasets as Topic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D008954:Models, Biological; D015742:Propofol / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol
keywords: allometric scaling; clearance; paediatric; pharmacokinetics; propofol