title: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Office of Blood Review & Research, Center for Biologic Evaluation and Research, Food and Drug Administration, Rockville, MD, USA. iftekhar.mahmood@fda.hhs.gov
authors.forename: I
authors.initials: I
authors.lastname: Mahmood
mesh_terms: D000328:Adult; D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D003029:Coagulants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005164:Factor IX / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005167:Factor VII / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005169:Factor VIII / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D015203:Reproducibility of Results
chemical_list: D003029:Coagulants; D011994:Recombinant Proteins; D005167:Factor VII; D005169:Factor VIII; D005164:Factor IX