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

BACKGROUND: Clonidine is used off-label in children but only limited pediatric pharmacokinetic data is 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 to 5 years were randomised for blood sampling. Clonidine was administered as a single intravenous bolus of 3 microg.kg(-1) intraoperatively. Blood samples were drawn at baseline, 5, 10, 15, 30, 60 min 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 to 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) .70kg(-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 to 5 years (mean difference 17% 95% CI:3-34%, p=0.02). 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 to 5 years, which was supported by pharmacodynamic observations.