The enantioselective population pharmacokinetics of intravenous ketorolac in children using a stereoselective assay suitable for microanalysis

Baba S. Mohammed, Thomas Engelhardt, Ahmed F. Hawwa, Garry A. Cameron, James S. McLay*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

KEY FINDINGS: 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 ).

Original languageEnglish
Pages (from-to)1179-1187
Number of pages9
JournalJournal of Pharmacy and Pharmacology
Volume67
Issue number9
Early online date16 Apr 2015
DOIs
Publication statusPublished - Sep 2015

Keywords

  • allometry
  • enantiomer
  • ketorolac
  • paediatric
  • pharmacokinetic
  • postoperative pain
  • tromethamine
  • infants
  • morphine
  • humans
  • paracetamol
  • metabolism
  • model
  • size
  • administration
  • intravenous
  • adolescent
  • body weight
  • child
  • child, preschool
  • female
  • infant
  • male
  • nonlinear dynamics
  • stereoisomerism

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