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Pharmacokinetics of clonidine after rectal administration in children
P A Lönnqvist1, H T Bergendahl, S Eksborg
1Department of Pediatric Anesthesiology and Intensive Care, St. Görans Pediatric Hospital, Karolinska Institute, Stockholm, Sweden.
Background:
alpha 2 Agonists have been shown to produce desirable effects when used as premedication or as an adjunct to general anesthesia in adult patients. Several of these beneficial effects (e.g., reduced anesthetic requirements and analgesia without respiratory depression) would be of great benefit in pediatric anesthesia. Information regarding the use of alpha 2 agonists in children is largely lacking. The aim of this study was to investigate the pharmacokinetics of clonidine after rectal administration in children.
Methods:
Ten ASA physical status 1 pediatric patients (age 14-48 months, weight 10-20 kg) received 2.5 micrograms.kg-1 of clonidine by the rectal route. Blood samples were taken during a 24-h period after the administration. Plasma levels of clonidine were analyzed by radioimmunoassay and subjected to a computer-aided curve-fitting program (PC Nonlin). To estimate the bioavailability of clonidine the results from the current study were compared with data from a previous study in which the same dose of clonidine was given to a similar patient population by the intravenous route.
Results:
Maximum plasma concentration was 0.77 ng.ml-1 (0.62-0.88), time to maximum plasma concentration 51 min (29-70), terminal half-life 12.5 h (8.7-19.5), and bioavailability 95% (73-119) (medians [95% confidence interval]). Plasma concentrations within the adult clinically effective range (0.2-2.0 ng.ml-1) were obtained within 10 min of administration.
Conclusions:
Rectal administration of 2.5 micrograms.kg-1 of clonidine in children, approximately 20 min before induction of anesthesia, achieves plasma concentrations within the range known to be clinically effective in adults.