title: Development of an optimal sampling schedule for children receiving ketamine for short-term procedural sedation and analgesia.
abstract: BACKGROUND
  Intravenous racemic ketamine is commonly administered for procedural sedation, although few pharmacokinetic studies have been conducted among children. Moreover, an optimal sampling schedule has not been derived to enable the conduct of pharmacokinetic studies that minimally inconvenience study participants.
  
  
  METHODS
  Concentration-time data were obtained from 57 children who received 1-1.5 mg·kg(-1) of racemic ketamine as an intravenous bolus. A population pharmacokinetic analysis was conducted using nonlinear mixed effects models, and the results were used as inputs to develop a D-optimal sampling schedule.
  
  
  RESULTS
  The pharmacokinetics of ketamine were described using a two-compartment model. The volume of distribution in the central and peripheral compartments were 20.5 l∙70 kg(-1) and 220 l∙70 kg(-1), respectively. The intercompartmental clearance and total body clearance were 87.3 and 87.9 l·h(-1) ∙70 kg(-1), respectively. Population parameter variability ranged from 34% to 98%. Initially, blood samples were drawn on 3-6 occasions spanning a range of 14-152 min after dosing. Using these data, we determined that four optimal sampling windows occur at 1-5, 5.5-7.5, 10-20, and 90-180 min after dosing. Monte Carlo simulations indicated that these sampling windows produced precise and unbiased ketamine pharmacokinetic parameter estimates.
  
  
  CONCLUSIONS
  An optimal sampling schedule was developed that allowed assessment of the pharmacokinetic parameters of ketamine among children requiring short-term procedural sedation.
authors.affiliation: Division of Clinical Pharmacology, Department of Paediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Catherine M T
authors.initials: CM
authors.lastname: Sherwin
authors.forename: Chris
authors.initials: C
authors.lastname: Stockmann
authors.forename: Kristin
authors.initials: K
authors.lastname: Grimsrud
authors.forename: David W
authors.initials: DW
authors.lastname: Herd
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Anderson
authors.forename: Michael G
authors.initials: MG
authors.lastname: Spigarelli
mesh_terms: D000698:Analgesia / Q000379:methods*; D000778:Anesthetics, Dissociative / Q000097:blood* / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007649:Ketamine / Q000097:blood* / Q000493:pharmacokinetics*; D008297:Male; D015233:Models, Statistical; D009010:Monte Carlo Method; D013997:Time Factors
chemical_list: D000778:Anesthetics, Dissociative; D007649:Ketamine
keywords: children; optimal sampling strategy; pharmacodynamics; pharmacokinetics