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Population pharmacokinetics of oxycodone: Premature neonates to adults

James D Morse1, Milan Sundermann1, Jacqueline A Hannam1

  • 1Department of Pharmacology & Clinical Pharmacology, The University of Auckland, Auckland, New Zealand.

Paediatric Anaesthesia
|September 1, 2021
PubMed

Insights

Oxycodone clearance matures significantly from infancy to adulthood, with total body weight being a key factor. This study quantifies these pharmacokinetic changes across the human lifespan for better dosing.

Area of Science:

  • Pharmacology
  • Pediatric Pharmacokinetics
  • Drug Metabolism

Background:

  • Oxycodone is a critical analgesic for acute postoperative pain in pediatric and adult populations.
  • Limited data exists on how age, body size, and fat mass influence oxycodone pharmacokinetics throughout life.

Purpose of the Study:

  • To quantify the pharmacokinetic parameters of oxycodone across the human lifespan.
  • To investigate the impact of covariates like age and body composition on oxycodone disposition.
  • To develop a population pharmacokinetic model for oxycodone.

Main Methods:

  • Analysis of pooled oxycodone time-concentration data from preterm neonates to adults.
  • Application of nonlinear mixed-effects models to pharmacokinetic data.
  • Utilizing theory-based allometry and a maturation function to describe pharmacokinetic variability.

Main Results:

  • A three-compartment model effectively described oxycodone disposition.
  • Total body weight was identified as the optimal covariate for scaling clearance and volume of distribution.
  • Absorption times varied significantly by administration route, with intramuscular being the fastest.

Conclusions:

  • Oxycodone clearance demonstrates significant maturation with age, reaching adult values by the first year of life.
  • Total body weight is a more appropriate descriptor for oxycodone clearance than fat-free mass.
  • These findings support optimized dosing strategies for oxycodone across diverse age groups.
Abstract

Keywords:
analgesiachildrenclearance maturationnonlinear mixed-effectsoxycodonepainpharmacokinetics

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