• Bettina N Nielsen, Brian J Anderson, Lars Falcon, Steen W Henneberg, Torsten Lauritsen, Erik Lomstein, Mogens Ydemann, and Arash Afshari.
• Department of Anaesthesia, The Juliane Marie Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
• Paediatr Anaesth. 2020 May 1; 30 (5): 607-613.

BackgroundClonidine is used off-label in children but only limited pediatric pharmacokinetic data are available for intravenously administered clonidine.ObjectivesTo 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.MethodsIn 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.ResultsData 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).ConclusionPharmacokinetic 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.© 2020 John Wiley & Sons Ltd.

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