Clonidine disposition in children; a population analysis

Paediatr Anaesth. 2007 Oct;17(10):924-33. doi: 10.1111/j.1460-9592.2007.02251.x.


Background: There are few data describing clonidine population pharmacokinetics in children (0-15 years) despite common use. Current pediatric data, described in terms of elimination half-life or C(max) and T(max), poorly explain variability in drug responses among individuals representative of those in whom the drug will be used clinically.

Methods: Published data from four studies investigating clonidine PK after intravenous (i.v.), rectal and epidural administration (n = 42) were combined with an open-label study undertaken to examine the pharmacokinetics of i.v. clonidine 1-2 microg x kg(-1) bolus in children after cardiac surgery (n = 41). A population pharmacokinetic analysis of clonidine time-concentration profiles (380 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 4 (sd 3.6 years, range 1 week-14 years) years and weight 17.8 (sd 12.6, range 2.8-60) 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) 14.6 (CV 35.1%) l x h(-1 )70 kg(-1), central volume of distribution (V1) 62.5 (71.1%) l 70 kg(-1), intercompartment clearance (Q) 157 (77.3%) l x h(-1) 70 kg(-1) and peripheral volume of distribution (V2) 119 (22.9%) l 70 kg(-1). Clearance at birth was 3.8 l x h(-1) 70 kg(-1) and matured with a half-time of 25.7 weeks to reach 82% adult rate by 1 year of age. The volumes of distribution, but not clearance, were increased after cardiac surgery (V1 123%, V2 126%). There was a lag time of 2.3 (CV 73.2%) min before absorption began in the rectum. The absorption half-life from the epidural space was slower than that from the rectum (0.98 CV 24.5% h vs 0.26 CV 32.3% h). The relative bioavailability of epidural and rectal clonidine was unity (F = 1).

Conclusions: Clearance in neonates is approximately one-third 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic alpha-Agonists / administration & dosage
  • Adrenergic alpha-Agonists / pharmacokinetics*
  • Age Factors
  • Anesthesia / methods*
  • Cardiac Surgical Procedures
  • Child
  • Child, Preschool
  • Clonidine / administration & dosage
  • Clonidine / pharmacokinetics*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Metabolic Clearance Rate
  • Time Factors


  • Adrenergic alpha-Agonists
  • Clonidine