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

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).