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Maturation of oxycodone pharmacokinetics in neonates and infants: Oxycodone and its metabolites in plasma and urine
Author(s) -
Kokki Merja,
Heikkinen Marja,
Välitalo Pyry,
Hautajärvi Heidi,
Hokkanen Juho,
Pitkänen Hanna,
Sankilampi Ulla,
Ranta VeliPekka,
Kokki Hannu
Publication year - 2017
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13164
Subject(s) - pharmacokinetics , oxycodone , medicine , oxymorphone , urine , gestational age , anesthesia , population , pediatrics , pharmacology , pregnancy , receptor , environmental health , biology , opioid , genetics
Aims 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. Methods 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 −1 during 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. Results 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. Conclusions 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.