Dexmedetomidine disposition in children: a population analysis.
BACKGROUND
There are few data describing dexmedetomidine population pharmacokinetics (PK) in children (0-15 years) despite increasing use.


METHODS
An open-label study was undertaken to examine the PK of i.v. dexmedetomidine 1-4 mug.kg(-1) bolus in children after cardiac surgery (n = 45). A population PK analysis of dexmedetomidine time-concentration profiles (148 observations) was undertaken using nonlinear mixed effects modeling. Estimates were standardized to a 70-kg adult using allometric size models.


RESULTS
Children had a mean age of 3.38 years (range 4 days to 14 years) and weight 15.1 kg (range 3.1-58.9 kg). A two-compartment disposition model with first order elimination was superior to a one-compartment model. Population parameter estimates (between subject variability) were clearance (CL) 39.2 (CV 30.36%) l.h(-1) per 70 kg, central volume of distribution (V1) 36.9 (69.49%) l per 70 kg, inter-compartment clearance (Q) 68.2 (37.6%) l.h(-1) per 70 kg and peripheral volume of distribution (V2) 69.9 (48.6%) l per 70 kg. Clearance at birth was 15.55 l.h(-1) per 70 kg and matured with a half-time of 46.5 weeks to reach 87% adult rate by 1 year of age. Simulation of an infusion of 1 mug.kg(-1) over 10 min followed by an infusion of 0.7 mug.kg(-1).h(-1) for 50 min suggested that children arouse from sedation at a plasma concentration of 0.304 mug.l(-1).


CONCLUSIONS
Clearance in neonates is approximately one-third of that described in adults, consistent with immature elimination pathways. Maintenance dosing, which is a function of clearance, should be reduced in neonates and infants when using a target concentration approach.
Potts
Amanda L
AL
University of Auckland, Auckland, New Zealand. a.potts@auckland.ac.nz
Warman
Guy R
GR
Anderson
Brian J
BJ
D000293:Adolescent; D000762:Anesthesia Recovery Period; D006348:Cardiac Surgical Procedures; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D016292:Procedural Sedation; D020927:Dexmedetomidine / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood / Q000493:pharmacokinetics*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008962:Models, Theoretical; D011153:Population
D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine