title: Maturation of oxycodone pharmacokinetics in neonates and infants: Oxycodone and its metabolites in plasma and urine.
abstract: This study aimed to characterize the pharmacokinetics of oxycodone and its major metabolites in infants and covered the age range between extremely preterm neonates and 2-year-old infants.
  
  
  
  Seventy-nine infants (gestational age 23-42 weeks; postnatal age 0-650 days) received intravenous oxycodone hydrochloride trihydrate at a dose of 0.1 mg kg-1during or after surgery. Three to seven blood samples were taken from each infant, and plasma concentrations of oxycodone, noroxycodone, oxymorphone, and noroxymorphone were quantified. The unconjugated forms of these compounds were determined in urine collected after up to 24 or 48 h from 25 infants. Pharmacokinetics was determined using noncompartmental analysis and reported for six clinically relevant age groups based on postmenstrual age.
  
  
  
  Oxycodone pharmacokinetics changed markedly with patient age. Preterm neonates were found to have the highest pharmacokinetic variability out of the study population. In extremely preterm neonates (n = 6) median of elimination half-life was 8.8 h (range 6.8-12.5), in preterm (n = 11) 7.4 h (4.2-11.6), and in older neonates (n = 22) 4.1 h (2.4-5.8), all of which were significantly longer than that in infants aged 6-24 months (n = 12) 2.0 h (1.7-2.6). Median renal clearance was fairly constant in all age groups, whereas non-renal clearance markedly increased with age. Noroxycodone was the major metabolite in plasma and urine.
  
  
  
  Oxycodone elimination is slower and pharmacokinetic variability more pronounced in neonates when compared to older infants. These findings highlight the importance of careful dose titration for neonates.
authors: Department of Anaesthesia and Operative Services, Kuopio University Hospital, Kuopio, Finland.|School of Medicine, University of Eastern Finland, Kuopio, Finland.
authors: Merja
authors: M
authors: Kokki
authors: Department of Paediatric Surgery, Kuopio University Hospital, Kuopio, Finland.
authors: Marja
authors: M
authors: Heikkinen
authors: Division of Pharmacology, Leiden University, Leiden, The Netherlands.
authors: Pyry
authors: P
authors: Välitalo
authors: Admescope Ltd, Oulu, Finland.
authors: Heidi
authors: H
authors: Hautajärvi
authors: Admescope Ltd, Oulu, Finland.
authors: Juho
authors: J
authors: Hokkanen
authors: Department of Anaesthesia and Operative Services, Kuopio University Hospital, Kuopio, Finland.|School of Medicine, University of Eastern Finland, Kuopio, Finland.
authors: Hanna
authors: H
authors: Pitkänen
authors: School of Medicine, University of Eastern Finland, Kuopio, Finland.|Department of Paediatrics, Kuopio University Hospital, Kuopio, Finland.
authors: Ulla
authors: U
authors: Sankilampi
authors: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors: Veli-Pekka
authors: VP
authors: Ranta
authors: Department of Anaesthesia and Operative Services, Kuopio University Hospital, Kuopio, Finland.|School of Medicine, University of Eastern Finland, Kuopio, Finland.
authors: Hannu
authors: H
authors: Kokki
mesh_terms: D000367:Age Factors; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002675:Child, Preschool; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D009019:Morphinans / Q000493:pharmacokinetics*; D010098:Oxycodone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D009019:Morphinans; C077256:noroxycodone; C526569:noroxymorphone; D010098:Oxycodone
keywords: infant; neonate; oxycodone; pharmacokinetics; preterm