Background: Oxycodone pharmacokinetics have been described in premature neonates through to obese adults. Covariate influences have been accounted for using allometry (size) and maturation of oxycodone clearance with age. The target concentration is dependent on pain intensity that may differ over pain duration or between individuals.
Methods: We assumed a target concentration of 35 mcg.L-1 (acceptable range ±20%) to be associated with adequate analgesia without increased risk of adverse effects from respiratory depression. Pharmacokinetic simulation was used to estimate dose in neonates through to obese adults given intravenous or parenteral oxycodone.
Results: There were 84% of simulated oxycodone concentrations within the acceptable range during maintenance dosing. Variability around the simulated target concentration decreased with age. The maturation of oxycodone clearance is reflected in changes to context-sensitive halftime where clearance is immature in neonates compared with older children and adults. The intravenous loading and maintenance doses for a typical 5-year-old child are 100 mcg.kg-1 and 33 mcg.kg-1 .h-1 . In a typical adult, the loading dose is 100 mcg.kg-1 and maintenance dose 23 mcg.kg-1 .h-1 .
Conclusion: Simulation was used to suggest loading and maintenance doses to attain an oxycodone concentration of 35 mcg.L-1 predicted in adults. Although the covariates age and weight contribute 92% variability for clearance, there remains variability accounting for 16% of concentrations outside the target range. Duration of analgesic effect after ceasing infusion is anticipated to be longer in neonates where context-sensitive halftime is greater than older children and adults.
Keywords: analgesia; children; oxycodone; pain; pharmacodynamics; pharmacokinetics; toxicity.
© 2021 John Wiley & Sons Ltd.