title: The enantioselective population pharmacokinetics of intravenous ketorolac in children using a stereoselective assay suitable for microanalysis.
abstract: OBJECTIVE
  To describe the effect of age and body size on enantiomer selective pharmacokinetic (PK) of intravenous ketorolac in children using a microanalytical assay.
  
  
  METHODS
  Blood samples were obtained at 0, 15 and 30 min and at 1, 2, 4, 6, 8 and 12 h after a weight-dependent dose of ketorolac. Enantiomer concentration was measured using a liquid chromatography tandem mass spectrometry method. Non-linear mixed-effect modelling was used to assess PK parameters.
  
  
  RESULTS
  Data from 11 children (1.7-15.6 years, weight 10.7-67.4 kg) were best described by a two-compartment model for R(+), S(-) and racemic ketorolac. Only weight (WT) significantly improved the goodness of fit. The final population models were CL = 1.5 × (WT/46)(0.75) , V1  = 8.2 × (WT/46), Q = 3.4 × (WT/46)(0.75) , V2  = 7.9 × (WT/46), CL = 2.98 × (WT/46), V1  = 13.2 × (WT/46), Q = 2.8 × (WT/46)(0.75) , V2  = 51.5 × (WT/46), and CL = 1.1 × (WT/46)(0.75) , V1  = 4.9 × (WT/46), Q = 1.7 × (WT/46)(0.75) and V2  = 6.3 × (WT/46)for R(+), S(-) and racemic ketorolac.
  
  
  CONCLUSIONS
  Only body weight influenced the PK parameters for R(+) and S(-) ketorolac. Using allometric size scaling significantly affected the clearances (CL, Q) and volumes of distribution (V1 , V2 ).
authors.affiliation: Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Baba S
authors.initials: BS
authors.lastname: Mohammed
authors.affiliation: Department of Anaesthesiology, Royal Aberdeen Children's Hospital, Aberdeen, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Engelhardt
authors.affiliation: School of Pharmacy, Aston University, Birmingham, UK.
authors.forename: Ahmed F
authors.initials: AF
authors.lastname: Hawwa
authors.affiliation: Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Garry A
authors.initials: GA
authors.lastname: Cameron
authors.affiliation: Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: James S
authors.initials: JS
authors.lastname: McLay
mesh_terms: D061605:Administration, Intravenous / Q000379:methods; D000293:Adolescent; D001835:Body Weight / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D020910:Ketorolac / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D017711:Nonlinear Dynamics; D013237:Stereoisomerism
chemical_list: D020910:Ketorolac
keywords: allometry; enantiomer; ketorolac; paediatric; pharmacokinetic