Abstract
Background: Intravenous ketorolac is commonly administered to children for the control of postoperative pain. An effect site EC50 for analgesia of 0.37 mg.L−1 is described in adults. Aims: The aim of this study was to review age- and weight-related effects on ketorolac pharmacokinetic parameters in children and current dosing schedules. Methods: Pooled intravenous ketorolac (0.5 mg.kg−1) concentration-time data in children aged 2 months to 16 years were analyzed using nonlinear mixed-effects models. Allometry was used to scale to a 70 kg person. Results: There were 64 children aged 2 months to 16 years (641 plasma concentrations) available for analysis. A two-compartment mammillary model was used to describe pharmacokinetics. Clearance was 2.53 (CV 45.9%) L.h−1.70 kg−1 and intercompartment clearance was 4.43 (CV 95.6%) L.h−1.70 kg−1. Both central (V1) and peripheral (V2) volumes of distribution decreased with age over the first few years of postnatal life to reach V1 6.89 (CV 30.3%) L.70 kg−1 and V2 5.53 (CV 47.6%) L.70 kg−1. Conclusion: Clearance, expressed as L.h−1.kg−1, decreased with age from infancy. A dosing regimen of 0.5 mg.kg−1 every 6 hours maintains a trough concentration larger than 0.37 mg.L−1 in children 9 months to 16 years of age. This dosing regimen is consistent with current recommendations.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 80-86 |
| Number of pages | 7 |
| Journal | Paediatric anaesthesia |
| Volume | 28 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2018 |
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Keywords
- analgesia
- child
- ketorolac
- nonlinear mixed-effects modelling
- pharmacokinetics
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Anesthesiology and Pain Medicine
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The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years : A population analysis. / McLay, James S.; Engelhardt, Thomas; Mohammed, Baba S.; Cameron, Gary; Cohen, Mindy N.; Galinkin, Jeffrey L.; Christians, Uwe; Avram, Michael J; Henthorn, Thomas K.; Dsida, Richard; Anderson, Brian J.
In: Paediatric anaesthesia, Vol. 28, No. 2, 01.02.2018, p. 80-86.Research output: Contribution to journal › Article
TY - JOUR
T1 - The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years
T2 - A population analysis
AU - McLay, James S.
AU - Engelhardt, Thomas
AU - Mohammed, Baba S.
AU - Cameron, Gary
AU - Cohen, Mindy N.
AU - Galinkin, Jeffrey L.
AU - Christians, Uwe
AU - Avram, Michael J
AU - Henthorn, Thomas K.
AU - Dsida, Richard
AU - Anderson, Brian J.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - Background: Intravenous ketorolac is commonly administered to children for the control of postoperative pain. An effect site EC50 for analgesia of 0.37 mg.L−1 is described in adults. Aims: The aim of this study was to review age- and weight-related effects on ketorolac pharmacokinetic parameters in children and current dosing schedules. Methods: Pooled intravenous ketorolac (0.5 mg.kg−1) concentration-time data in children aged 2 months to 16 years were analyzed using nonlinear mixed-effects models. Allometry was used to scale to a 70 kg person. Results: There were 64 children aged 2 months to 16 years (641 plasma concentrations) available for analysis. A two-compartment mammillary model was used to describe pharmacokinetics. Clearance was 2.53 (CV 45.9%) L.h−1.70 kg−1 and intercompartment clearance was 4.43 (CV 95.6%) L.h−1.70 kg−1. Both central (V1) and peripheral (V2) volumes of distribution decreased with age over the first few years of postnatal life to reach V1 6.89 (CV 30.3%) L.70 kg−1 and V2 5.53 (CV 47.6%) L.70 kg−1. Conclusion: Clearance, expressed as L.h−1.kg−1, decreased with age from infancy. A dosing regimen of 0.5 mg.kg−1 every 6 hours maintains a trough concentration larger than 0.37 mg.L−1 in children 9 months to 16 years of age. This dosing regimen is consistent with current recommendations.
AB - Background: Intravenous ketorolac is commonly administered to children for the control of postoperative pain. An effect site EC50 for analgesia of 0.37 mg.L−1 is described in adults. Aims: The aim of this study was to review age- and weight-related effects on ketorolac pharmacokinetic parameters in children and current dosing schedules. Methods: Pooled intravenous ketorolac (0.5 mg.kg−1) concentration-time data in children aged 2 months to 16 years were analyzed using nonlinear mixed-effects models. Allometry was used to scale to a 70 kg person. Results: There were 64 children aged 2 months to 16 years (641 plasma concentrations) available for analysis. A two-compartment mammillary model was used to describe pharmacokinetics. Clearance was 2.53 (CV 45.9%) L.h−1.70 kg−1 and intercompartment clearance was 4.43 (CV 95.6%) L.h−1.70 kg−1. Both central (V1) and peripheral (V2) volumes of distribution decreased with age over the first few years of postnatal life to reach V1 6.89 (CV 30.3%) L.70 kg−1 and V2 5.53 (CV 47.6%) L.70 kg−1. Conclusion: Clearance, expressed as L.h−1.kg−1, decreased with age from infancy. A dosing regimen of 0.5 mg.kg−1 every 6 hours maintains a trough concentration larger than 0.37 mg.L−1 in children 9 months to 16 years of age. This dosing regimen is consistent with current recommendations.
KW - analgesia
KW - child
KW - ketorolac
KW - nonlinear mixed-effects modelling
KW - pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=85040793885&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040793885&partnerID=8YFLogxK
U2 - 10.1111/pan.13302
DO - 10.1111/pan.13302
M3 - Article
C2 - 29266539
AN - SCOPUS:85040793885
VL - 28
SP - 80
EP - 86
JO - Paediatric Anaesthesia
JF - Paediatric Anaesthesia
SN - 1155-5645
IS - 2
ER -