Allometric extrapolation of factors VII, VIII and IX clearance in children from adults

Abstract

Background: There are situations where a pharmacokinetic (PK) study may not be possible in children, especially in neonates and infants. Under these circumstances, one would like to extrapolate PK parameters from adults or older children to neonates and infants. Allometric scaling is a method which can be used for PK extrapolation from adults to children. Objectives: The objective of this study was to evaluate the predictive performance of an allometric model for the prediction of clearance of three coagulation factors in children from adult clearance. Methods: Clearance values for three coagulation factors (rVIIa, rVIII and rIX) for adults and children were obtained from the literature. The allometric model was developed from adult data and then the model was used to predict clearance of the coagulation factors in individual child. The predicted clearance value was then compared with the observed clearance value in that child. Results: The results of the study indicated that the CL of the three coagulation factors tested in this study could be predicted with accuracy (≤30% prediction error) in most of the children from the allometric model developed from adults. Conclusions: The study indicated that allometric scaling could be applied to predict the CL of coagulation factors in children from adults with accuracy. The predicted clearance can then be used to select a dose to initiate a clinical trial (pharmacokinetics, safety and efficacy) in children. © 2012 International Society on Thrombosis and Haemostasis.