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Pharmacokinetics of an intravenous bolus dose of clonidine in children undergoing surgery

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@article{648b68a6e653423fb10d8ed45943558b,
title = "Pharmacokinetics of an intravenous bolus dose of clonidine in children undergoing surgery",
abstract = "BACKGROUND: Clonidine is used off-label in children but only limited pediatric pharmacokinetic data are available for intravenously administered clonidine.OBJECTIVES: To determine pharmacokinetic parameter estimates of clonidine in healthy children undergoing surgery and to investigate age-related differences. Furthermore, to investigate possible pharmacokinetic differences of clonidine between this group of children and a cohort with cardiac diseases.METHODS: In a randomized placebo-controlled trial (The PREVENT AGITATION trial), blood samples for clonidine pharmacokinetic analysis were collected in a proportion of the enrolled patients. Healthy children with ASA score 1-2 in the age-groups 1 to <2 years and 2-5 years were randomized for blood sampling. Clonidine was administered as a single intravenous bolus of 3 µg/kg intraoperatively. Blood samples were drawn at baseline, 5, 10, 15, 30, 60 minutes after dosing and additionally every hour until discharge from the PACU. Clonidine analysis was performed on liquid chromatography-mass spectrometry.RESULTS: Data form eighteen children were available for pharmacokinetic analysis (ASA I; male/female: 17/1; age: 1-5 years; weight 8.7-24 kg). Population parameter estimates for the 2-compartment model were similar to previous published data for children who underwent cardiac surgery. A pooled analysis including data from 59 children indicated clearance of 14.4 L h -1 70 kg -1 and volume of distribution of 192.6 L 70 kg -1 . No age-related pharmacokinetic differences and no difference in time from administration of study medication to awakening were found. Children 1 to <2 years had a shorter PACU stay than children 2-5 years (mean difference 17{\%} 95{\%} CI:3{\%}-34{\%}, P = .02). CONCLUSION: Pharmacokinetic parameter estimates were similar for children undergoing general surgery and cardiac surgery given a single dose of intravenous clonidine. These results indicated that no dose reduction is needed in children aged 1 to <2 years compared with those 2-5 years, which was supported by pharmacodynamic observations.",
keywords = "children, clonidine, pharmacokinetics, surgery",
author = "Nielsen, {Bettina N} and Anderson, {Brian J} and Lars Falcon and Henneberg, {Steen W} and Torsten Lauritsen and Erik Lomstein and Mogens Ydemann and Arash Afshari",
note = "{\circledC} 2020 John Wiley & Sons Ltd.",
year = "2020",
month = "5",
doi = "10.1111/pan.13856",
language = "English",
volume = "30",
pages = "607--613",
journal = "Paediatric Anaesthesia Online",
issn = "1460-9592",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "5",

}

RIS

TY - JOUR

T1 - Pharmacokinetics of an intravenous bolus dose of clonidine in children undergoing surgery

AU - Nielsen, Bettina N

AU - Anderson, Brian J

AU - Falcon, Lars

AU - Henneberg, Steen W

AU - Lauritsen, Torsten

AU - Lomstein, Erik

AU - Ydemann, Mogens

AU - Afshari, Arash

N1 - © 2020 John Wiley & Sons Ltd.

PY - 2020/5

Y1 - 2020/5

N2 - BACKGROUND: Clonidine is used off-label in children but only limited pediatric pharmacokinetic data are available for intravenously administered clonidine.OBJECTIVES: To determine pharmacokinetic parameter estimates of clonidine in healthy children undergoing surgery and to investigate age-related differences. Furthermore, to investigate possible pharmacokinetic differences of clonidine between this group of children and a cohort with cardiac diseases.METHODS: In a randomized placebo-controlled trial (The PREVENT AGITATION trial), blood samples for clonidine pharmacokinetic analysis were collected in a proportion of the enrolled patients. Healthy children with ASA score 1-2 in the age-groups 1 to <2 years and 2-5 years were randomized for blood sampling. Clonidine was administered as a single intravenous bolus of 3 µg/kg intraoperatively. Blood samples were drawn at baseline, 5, 10, 15, 30, 60 minutes after dosing and additionally every hour until discharge from the PACU. Clonidine analysis was performed on liquid chromatography-mass spectrometry.RESULTS: Data form eighteen children were available for pharmacokinetic analysis (ASA I; male/female: 17/1; age: 1-5 years; weight 8.7-24 kg). Population parameter estimates for the 2-compartment model were similar to previous published data for children who underwent cardiac surgery. A pooled analysis including data from 59 children indicated clearance of 14.4 L h -1 70 kg -1 and volume of distribution of 192.6 L 70 kg -1 . No age-related pharmacokinetic differences and no difference in time from administration of study medication to awakening were found. Children 1 to <2 years had a shorter PACU stay than children 2-5 years (mean difference 17% 95% CI:3%-34%, P = .02). CONCLUSION: Pharmacokinetic parameter estimates were similar for children undergoing general surgery and cardiac surgery given a single dose of intravenous clonidine. These results indicated that no dose reduction is needed in children aged 1 to <2 years compared with those 2-5 years, which was supported by pharmacodynamic observations.

AB - BACKGROUND: Clonidine is used off-label in children but only limited pediatric pharmacokinetic data are available for intravenously administered clonidine.OBJECTIVES: To determine pharmacokinetic parameter estimates of clonidine in healthy children undergoing surgery and to investigate age-related differences. Furthermore, to investigate possible pharmacokinetic differences of clonidine between this group of children and a cohort with cardiac diseases.METHODS: In a randomized placebo-controlled trial (The PREVENT AGITATION trial), blood samples for clonidine pharmacokinetic analysis were collected in a proportion of the enrolled patients. Healthy children with ASA score 1-2 in the age-groups 1 to <2 years and 2-5 years were randomized for blood sampling. Clonidine was administered as a single intravenous bolus of 3 µg/kg intraoperatively. Blood samples were drawn at baseline, 5, 10, 15, 30, 60 minutes after dosing and additionally every hour until discharge from the PACU. Clonidine analysis was performed on liquid chromatography-mass spectrometry.RESULTS: Data form eighteen children were available for pharmacokinetic analysis (ASA I; male/female: 17/1; age: 1-5 years; weight 8.7-24 kg). Population parameter estimates for the 2-compartment model were similar to previous published data for children who underwent cardiac surgery. A pooled analysis including data from 59 children indicated clearance of 14.4 L h -1 70 kg -1 and volume of distribution of 192.6 L 70 kg -1 . No age-related pharmacokinetic differences and no difference in time from administration of study medication to awakening were found. Children 1 to <2 years had a shorter PACU stay than children 2-5 years (mean difference 17% 95% CI:3%-34%, P = .02). CONCLUSION: Pharmacokinetic parameter estimates were similar for children undergoing general surgery and cardiac surgery given a single dose of intravenous clonidine. These results indicated that no dose reduction is needed in children aged 1 to <2 years compared with those 2-5 years, which was supported by pharmacodynamic observations.

KW - children

KW - clonidine

KW - pharmacokinetics

KW - surgery

U2 - 10.1111/pan.13856

DO - 10.1111/pan.13856

M3 - Journal article

VL - 30

SP - 607

EP - 613

JO - Paediatric Anaesthesia Online

JF - Paediatric Anaesthesia Online

SN - 1460-9592

IS - 5

ER -

ID: 59610201