title: Population pharmacokinetics of nalbuphine after surgery in children.
abstract: BACKGROUND
  Nalbuphine is an opioid analgesic agent widely used for control of mild-to-severe pain. However, limited data are available on the pharmacokinetics of this drug in children. The aim of this study was to characterize the population pharmacokinetics of nalbuphine in patients with ages ranging from 1 to 11 yr and to identify patient characteristics partially explaining inter-individual variability in nalbuphine pharmacokinetic parameters.
  
  
  METHODS
  Twenty-two children were included in this study. They received nalbuphine after surgery by continuous infusion (loading dose, 0.2 mg kg(-1) over 10 min followed by continuous infusion of 0.8 mg kg(-1) over 24 h). If pain relief was not adequate, 0.1 mg kg(-1) bolus doses were allowed in 10 min. Eleven blood samples were collected per patient. The data were analysed by non-linear mixed-effect modelling with the use of a two-compartment structural model.
  
  
  RESULTS
  Twenty patients completed the study. In the final model, the parameter values were standardized for a body weight of 70 kg using an allometric model. Population parameter estimates were: clearance 130 litre h(-1) 70 kg(-1), inter-compartment clearance 75.6 litre h(-1) 70 kg(-1), central volume of distribution 210 litre 70 kg(-1), and peripheral volume of distribution 151 litre 70 kg(-1). In the children of this study, total clearance expressed in litre h(-1) kg(-1) decreased significantly with increasing age and the elimination half-life significantly increased.
  
  
  CONCLUSIONS
  The allometric power model developed in this study best reflected the data and may be useful for dose adjustment.
authors.affiliation: Pharmacokinetic Laboratory, Faculty of Pharmacy, BP 14491, Montpellier I University, 15 Avenue Ch. Flahault, 34093 Montpellier Cedex 5, France. fbressolle@aol.com
authors.forename: F
authors.initials: F
authors.lastname: Bressolle
authors.forename: S
authors.initials: S
authors.lastname: Khier
authors.forename: A
authors.initials: A
authors.lastname: Rochette
authors.forename: J M
authors.initials: JM
authors.lastname: Kinowski
authors.forename: C
authors.initials: C
authors.lastname: Dadure
authors.forename: X
authors.initials: X
authors.lastname: Capdevila
mesh_terms: D000375:Aging / Q000097:blood; D000701:Analgesics, Opioid / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001835:Body Weight / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D018662:Fundoplication; D005764:Gastroesophageal Reflux / Q000601:surgery; D006801:Humans; D007223:Infant; D010535:Laparoscopy; D008297:Male; D008954:Models, Biological; D009266:Nalbuphine / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010149:Postoperative Pain / Q000097:blood* / Q000517:prevention & control; D011182:Postoperative Care / Q000379:methods
chemical_list: D000701:Analgesics, Opioid; D009266:Nalbuphine