title: Preliminary assessment of zolpidem pharmacokinetics in pediatric burn patients.
abstract: OBJECTIVE
  Severely burned patients frequently experience sleep fragmentation and insomnia. This study evaluated the population pharmacokinetics of the sleep-enhancing agent zolpidem among burned children.
  
  
  METHODS
  Zolpidem was administered according to the following age-based dosing schedule: 2.5 mg per dose for 2-4 year olds, 5.0 mg per dose for 5-10 year olds, and 10 mg per dose for older than 10 years. Serum samples were collected before and 1, 2, 4, 5, 6, and 8 hours after dosing. The population pharmacokinetic analysis modeled zolpidem concentrations using nonlinear mixed effects models.
  
  
  RESULTS
  Eleven patients with a mean (±SD) age of 8.3 ± 4.0 years and a mean total burn surface area of 56% ± 22% were recruited. Seventy-three zolpidem concentrations were measured with a mean Cmax of 291 ± 140 ng/mL. A 2-compartment model with first-order absorption best described the data. Zolpidem clearance was estimated at 0.03 L·h(-1)·kg(-1) (relative standard error, 55%) and increased with body weight (P < 0.05). The central compartment volume of distribution was estimated at 0.05 L/kg (relative standard error, 25%), which was inversely related to the proportion of the body surface with third-degree burns (P < 0.001).
  
  
  CONCLUSIONS
  A population pharmacokinetic model has been developed that reliably characterized the pharmacokinetic parameters of zolpidem when used as a sleep-enhancing agent among pediatric burn patients. Additional studies are needed to link this pharmacokinetic model with pharmacodynamic data, which may include an assessment of the effects of higher zolpidem doses and/or more frequent administration upon sleep architecture.
authors.affiliation: *Division of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City; †James L. Winkle College of Pharmacy, University of Cincinnati; ‡The Shriners Hospitals for Children; and §Department of Surgery, University of Cincinnati, OH.
authors.forename: Chris
authors.initials: C
authors.lastname: Stockmann
authors.forename: Catherine M T
authors.initials: CM
authors.lastname: Sherwin
authors.forename: Whitney
authors.initials: W
authors.lastname: Buterbaugh
authors.forename: Michael G
authors.initials: MG
authors.lastname: Spigarelli
authors.forename: Michele M
authors.initials: MM
authors.lastname: Gottschlich
authors.forename: Daniel
authors.initials: D
authors.lastname: Healy
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kagan
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015992:Body Mass Index; D002056:Burns / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D011725:Pyridines / Q000493:pharmacokinetics*; D000077334:Zolpidem
chemical_list: D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem