期刊
JOURNAL OF PHARMACY AND PHARMACOLOGY
卷 67, 期 9, 页码 1179-1187出版社
WILEY-BLACKWELL
DOI: 10.1111/jphp.12418
关键词
allometry; enantiomer; ketorolac; paediatric; pharmacokinetic
资金
- 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
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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