Pharmacokinetics of single-dose intravenous ketorolac in infants aged 2-11 months
BACKGROUND: Ketorolac is a parenterally available nonsteroidal antiinflammatory drug that nonselectively inhibits cyclooxygenase. Ketorolac is an attractive alternative to opioids in the pediatric population because of its favorable side effect profile; it provides postoperative analgesia similar to morphine, but is associated with significantly less respiratory depression, pruritus, and emesis. Despite the efficacy of ketorolac in young patients, there are minimal data to characterize the pharmacokinetic variables of ketorolac in infants younger than 6 months.
METHODS: In this study, 17 infants younger than 1 year old, without renal or liver disease, undergoing elective surgery received a single-dose of IV ketorolac 0.5 mg/kg. Blood was sampled at 0, 5, 10, 15, 30, 60, and 120 minutes, and at 4, 6, 12, and 24 hours. Ketorolac levels were analyzed using a specific and validated high-performance liquid chromatography method with mass spectrometry (LC-LC/MS/MS). Pharmacokinetic analysis of individual subjects and population pharmacokinetic modeling was performed using SAAM II and PopKinetics, respectively (SAAM Institute, University of Washington).
RESULTS: Characterization of pharmacokinetic parameters was possible in 14 subjects. The data were best described by a 2-compartment model. Estimated individual parameters were clearance 1.49 ± 1.12 mL/min/kg, Vss (volume of distribution at steady state) 0.31 ± 0.11 L/kg, and half-life of 236 ± 169 minutes. Estimated population pharmacokinetic parameters were clearance 1.52 mL/min/kg and Vss 0.29 L/kg. There was a trend toward lower clearances in younger patients.
CONCLUSION: This is the first report of individualized pharmacokinetic parameters of ketorolac in children in which the majority of subjects were younger than 6 months old.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2011 |
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| Erschienen: |
2011 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:112 |
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| Enthalten in: |
Anesthesia and analgesia - 112(2011), 3 vom: 04. März, Seite 655-60 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cohen, Mindy N [VerfasserIn] |
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| Links: |
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| Themen: |
Comparative Study |
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| Anmerkungen: |
Date Completed 21.04.2011 Date Revised 20.11.2014 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1213/ANE.0b013e3182075d04 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM205044956 |
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| 500 | |a Date Revised 20.11.2014 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Ketorolac is a parenterally available nonsteroidal antiinflammatory drug that nonselectively inhibits cyclooxygenase. Ketorolac is an attractive alternative to opioids in the pediatric population because of its favorable side effect profile; it provides postoperative analgesia similar to morphine, but is associated with significantly less respiratory depression, pruritus, and emesis. Despite the efficacy of ketorolac in young patients, there are minimal data to characterize the pharmacokinetic variables of ketorolac in infants younger than 6 months | ||
| 520 | |a METHODS: In this study, 17 infants younger than 1 year old, without renal or liver disease, undergoing elective surgery received a single-dose of IV ketorolac 0.5 mg/kg. Blood was sampled at 0, 5, 10, 15, 30, 60, and 120 minutes, and at 4, 6, 12, and 24 hours. Ketorolac levels were analyzed using a specific and validated high-performance liquid chromatography method with mass spectrometry (LC-LC/MS/MS). Pharmacokinetic analysis of individual subjects and population pharmacokinetic modeling was performed using SAAM II and PopKinetics, respectively (SAAM Institute, University of Washington) | ||
| 520 | |a RESULTS: Characterization of pharmacokinetic parameters was possible in 14 subjects. The data were best described by a 2-compartment model. Estimated individual parameters were clearance 1.49 ± 1.12 mL/min/kg, Vss (volume of distribution at steady state) 0.31 ± 0.11 L/kg, and half-life of 236 ± 169 minutes. Estimated population pharmacokinetic parameters were clearance 1.52 mL/min/kg and Vss 0.29 L/kg. There was a trend toward lower clearances in younger patients | ||
| 520 | |a CONCLUSION: This is the first report of individualized pharmacokinetic parameters of ketorolac in children in which the majority of subjects were younger than 6 months old | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Ketorolac |2 NLM | |
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| 700 | 1 | |a Christians, Uwe |e verfasserin |4 aut | |
| 700 | 1 | |a Henthorn, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Vu Tran, Zung |e verfasserin |4 aut | |
| 700 | 1 | |a Moll, Vanessa |e verfasserin |4 aut | |
| 700 | 1 | |a Zuk, Jeannie |e verfasserin |4 aut | |
| 700 | 1 | |a Galinkin, Jeffrey |e verfasserin |4 aut | |
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