title: Potential pharmacokinetic basis for zolpidem dosing in children with sleep difficulties.
abstract: The pharmacokinetics of zolpidem was assessed in this open-label, dose-escalation study in children with insomnia. Twenty-one children, seven per age group (2-6, >6 to 12, >12 to 18 years), received a single dose of zolpidem at one of the three dose levels (0.125, 0.25, or 0.50 mg/kg (20 mg maximum dose)). Multiple pharmacokinetic measures were assessed at nine post-dose intervals and pharmacodynamics was assessed by polysomnography and actigraphy. Significant pharmacokinetic effects by dose were observed only as linear increases in maximum concentration (C(max), P<0.001) and area under the plasma concentration-time curve (AUC, P<0.001). Significant pharmacokinetic effects by age group included an increase in AUC (P=0.02), half-life (P=0.04), and mean residence time (P=0.01), whereas total body clearance decreased (P=0.01) and steady-state volume of distribution was variable. Pharmacodynamic measures were independent of the pharmacokinetic estimates. Overall, zolpidem was well tolerated and a pediatric dose of 0.25 mg/kg is recommended for future efficacy studies.
authors.affiliation: Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, Ohio, USA. Jeffrey.Blumer@UHhospitals.org
authors.forename: J L
authors.initials: JL
authors.lastname: Blumer
authors.forename: M D
authors.initials: MD
authors.lastname: Reed
authors.forename: F
authors.initials: F
authors.lastname: Steinberg
authors.forename: M A
authors.initials: MA
authors.lastname: O'Riordan
authors.forename: C L
authors.initials: CL
authors.lastname: Rosen
authors.forename: M A
authors.initials: MA
authors.lastname: Springer
authors.forename: M
authors.initials: M
authors.lastname: Christensen
authors.forename: D
authors.initials: D
authors.lastname: Glaze
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000704:Analysis of Variance; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D000077334:Zolpidem
chemical_list: D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem