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The enantioselective population pharmacokinetics of intravenous ketorolac in children using a stereoselective assay suitable for microanalysis.
- Source :
-
The Journal of pharmacy and pharmacology [J Pharm Pharmacol] 2015 Sep; Vol. 67 (9), pp. 1179-87. Date of Electronic Publication: 2015 Apr 16. - Publication Year :
- 2015
-
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.<br />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.<br />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.<br />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 ).<br /> (© 2015 Royal Pharmaceutical Society.)
Details
- Language :
- English
- ISSN :
- 2042-7158
- Volume :
- 67
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacy and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 25880462
- Full Text :
- https://doi.org/10.1111/jphp.12418