Maturation of Oxycodone Pharmacokinetics in Neonates and Infants : a Population Pharmacokinetic Model of Three Clinical Trials

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Valitalo , P , Kokki , M , Ranta , V-P , Olkkola , K T , Hooker , A C & Kokki , H 2017 , ' Maturation of Oxycodone Pharmacokinetics in Neonates and Infants : a Population Pharmacokinetic Model of Three Clinical Trials ' , Pharmaceutical Research , vol. 34 , no. 5 , pp. 1125-1133 . https://doi.org/10.1007/s11095-017-2122-6

Title: Maturation of Oxycodone Pharmacokinetics in Neonates and Infants : a Population Pharmacokinetic Model of Three Clinical Trials
Author: Valitalo, Pyry; Kokki, Merja; Ranta, Veli-Pekka; Olkkola, Klaus T.; Hooker, Andrew C.; Kokki, Hannu
Contributor organization: Clinicum
Anestesiologian yksikkö
Department of Diagnostics and Therapeutics
HUS Perioperative, Intensive Care and Pain Medicine
Date: 2017-05
Language: eng
Number of pages: 9
Belongs to series: Pharmaceutical Research
ISSN: 0724-8741
DOI: https://doi.org/10.1007/s11095-017-2122-6
URI: http://hdl.handle.net/10138/234743
Abstract: Purpose 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. Methods 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. Results 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. Conclustions 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.
Subject: analgesic
opioid. infant
extremely premature
oxycodone
pain
pharmacokinetics
DEVELOPMENTAL PHARMACOKINETICS
CHILDREN
METABOLITES
MORPHINE
116 Chemical sciences
317 Pharmacy
Peer reviewed: Yes
Rights: unspecified
Usage restriction: openAccess
Self-archived version: publishedVersion


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