Journal
JOURNAL OF PHARMACY AND PHARMACOLOGY
Volume 67, Issue 9, Pages 1179-1187Publisher
WILEY-BLACKWELL
DOI: 10.1111/jphp.12418
Keywords
allometry; enantiomer; ketorolac; paediatric; pharmacokinetic
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Funding
- Scottish Children Research Network (ScotCRN), a centre for mounting clinical trials and addressing the knowledge gaps in support of the effective and safe use of medicines in children
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ObjectiveTo describe the effect of age and body size on enantiomer selective pharmacokinetic (PK) of intravenous ketorolac in children using a microanalytical assay. MethodsBlood samples were obtained at 0, 15 and 30min and at 1, 2, 4, 6, 8 and 12h 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 findingsData from 11 children (1.7-15.6 years, weight 10.7-67.4kg) 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=1.5x(WT/46)(0.75), V-1=8.2x(WT/46), Q=3.4x(WT/46)(0.75), V-2=7.9x(WT/46), CL=2.98x(WT/46), V-1=13.2x(WT/46), Q=2.8x(WT/46)(0.75), V-2=51.5x(WT/46), and CL=1.1x(WT/46)(0.75), V-1=4.9x(WT/46), Q=1.7x(WT/46)(0.75) and V-2=6.3x(WT/46)for R(+), S(-) and racemic ketorolac. ConclusionsOnly 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 (V-1, V-2).
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