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. 2021 Dec;31(12):1332-1339.
doi: 10.1111/pan.14283. Epub 2021 Sep 12.

Population pharmacokinetics of oxycodone: Premature neonates to adults

James D Morse  1 , Milan Sundermann  1 , Jacqueline A Hannam  1 , Hannu Kokki  2 , Merja Kokki  3 , Brian J Anderson  4
Affiliations

Population pharmacokinetics of oxycodone: Premature neonates to adults

James D Morse et al. Paediatr Anaesth. 2021 Dec.

Abstract

Background: Oxycodone is used in children and adults for the control of acute postoperative pain. Covariate influences such as age, size, and fat mass on oxycodone pharmacokinetic parameters over the human lifespan are poorly quantified.

Methods: Pooled oxycodone time-concentration profiles were available from preterm neonates to adults. Data from intravenous, intramuscular, buccal, and epidural formulations were analyzed using nonlinear mixed-effects models. Normal fat mass was used to determine the influence of fat on oxycodone pharmacokinetics. Theory-based allometry was used to scale pharmacokinetic parameters to a 70 kg individual. A maturation function described the increase in clearance in neonates and infants.

Results: There were 237 subjects (24 weeks postmenstrual age to 75 years; 0.44-110 kg) providing 1317 plasma concentrations. A three-compartment model with first-order elimination best described oxycodone disposition. Population parameter estimates were clearance (CL) 48.6 L.h-1 .70 kg-1 (CV 71%); intercompartmental clearances (Q2) 220 L.h-1 .70 kg-1 (CV 64%); Q3 1.45 L.h-1 .70 kg-1 ; volume of distribution in the central compartment (V1) 98.2 L.70 kg-1 (CV 76%); rapidly equilibrating peripheral compartment (V2) 90.1 L. 70 kg-1 (CV 76%); slow equilibrating peripheral compartment (V3) 28.9 L.70 kg-1 . Total body weight was the best size descriptor for clearances and volumes. Absorption halftimes (TABS ) were: 1.1 minutes for intramuscular, 70 minutes for epidural, 82 minutes for nasogastric, and 159.6 minutes for buccal administration routes. The relative bioavailability after nasogastric administration was 0.673 with a lag time of 8.7 minutes.

Conclusions: Clearance matured with age; 8% of the typical adult value at 24 weeks postmenstrual age, 33% in a term neonate and reached 90% of the adult clearance value by the end of the first year of life. Allometric scaling using total body weight was the better size descriptor of oxycodone clearance than fat-free mass.

Keywords: analgesia; children; clearance maturation; nonlinear mixed-effects; oxycodone; pain; pharmacokinetics.

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References

REFERENCES

    1. Landwehr C, Richardson J, Bint L, et al. Cross-sectional survey of off-label and unlicensed prescribing for inpatients at a paediatric teaching hospital in Western Australia. PLoS One. 2019;14:e0210237.
    1. Moradi M, Esmaeili S, Shoar S, et al. Use of oxycodone in pain management. Anesth Pain Med. 2012;1:262-264.
    1. Lindell-Osuagwu L, Hakkarainen M, Sepponen K, et al. Prescribing for off-label use and unauthorized medicines in three paediatric wards in Finland, the status before and after the European Union Paediatric Regulation. J Clin Pharm Ther. 2014;39:144-153.
    1. Shum S, Isoherranen N. Human Fetal Liver Metabolism of Oxycodone Is Mediated by CYP3A7. AAPS J. 2021;23:24.
    1. Balyan R, Mecoli M, Venkatasubramanian R, et al. CYP2D6 pharmacogenetic and oxycodone pharmacokinetic association study in pediatric surgical patients. Pharmacogenomics. 2017;18:337-348.

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