title: Maturation of Oxycodone Pharmacokinetics in Neonates and Infants: a Population Pharmacokinetic Model of Three Clinical Trials.
abstract: The aim of the current population pharmacokinetic study was to quantify oxycodone pharmacokinetics in children ranging from preterm neonates to children up to 7 years of age.
  
  
  
  Data on intravenous or intramuscular oxycodone administration were obtained from three previously published studies (n = 119). The median [range] postmenstrual age of the subjects was 299 days [170 days-7.8 years]. A population pharmacokinetic model was built using 781 measurements of oxycodone plasma concentration. The model was used to simulate repeated intravenous oxycodone administration in four representative infants covering the age range from an extremely preterm neonate to 1-year old infant.
  
  
  
  The rapid maturation of oxycodone clearance was best described with combined allometric scaling and maturation function. Central and peripheral volumes of distribution were nonlinearly related to bodyweight. The simulations on repeated intravenous administration in virtual patients indicated that oxycodone plasma concentration can be kept between 10 and 50 ng/ml with a high probability when the maintenance dose is calculated using the typical clearance and the dose interval is 4 h.
  
  
  
  Oxycodone clearance matures rapidly after birth, and between-subject variability is pronounced in neonates. The pharmacokinetic model developed may be used to evaluate different multiple dosing regimens, but the safety of repeated doses should be ensured.
authors.affiliation: Division of Pharmacology, Leiden University, Leiden, The Netherlands.
authors.forename: Pyry
authors.initials: P
authors.lastname: Välitalo
authors.affiliation: Department of Anesthesia and Operative Services, Kuopio University Hospital, PO Box 100, FI-70029, Kuopio, Finland.|School of Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Merja
authors.initials: M
authors.lastname: Kokki
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Veli-Pekka
authors.initials: VP
authors.lastname: Ranta
authors.affiliation: Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Olkkola
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Hooker
authors.affiliation: Department of Anesthesia and Operative Services, Kuopio University Hospital, PO Box 100, FI-70029, Kuopio, Finland. hannu.kokki@uef.fi.|School of Medicine, University of Eastern Finland, Kuopio, Finland. hannu.kokki@uef.fi.
authors.forename: Hannu
authors.initials: H
authors.lastname: Kokki
mesh_terms: D000367:Age Factors; D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D001835:Body Weight / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D007262:Infusions, Intravenous / Q000379:methods; D008657:Metabolic Clearance Rate / Q000502:physiology; D010098:Oxycodone / Q000493:pharmacokinetics*
chemical_list: D000701:Analgesics, Opioid; D010098:Oxycodone
keywords: analgesic, opioid; infant, extremely premature; oxycodone; pain; pharmacokinetics