Article date: January 2014
By: Chenguang Wang, Karel Allegaert, Mariska Y. M. Peeters, Dick Tibboel, Meindert Danhof, Catherijne A. J. Knibbe, in Volume 77, Issue 1, pages 149-159
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.
DOI: 10.1111/bcp.12180
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