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Oxycodone target concentration dosing for acute pain in children
James D Morse1, Jacqueline A Hannam1, Brian J Anderson2
1Department of Pharmacology & Clinical Pharmacology, The University of Auckland, Auckland, New Zealand.
Insights
This study simulated oxycodone dosing to achieve target concentrations for adequate analgesia across all ages. Dosing recommendations were developed, noting variability and age-dependent clearance impact on effectiveness.
Area of Science:
- Pharmacology
- Pediatric Anesthesiology
- Clinical Pharmacy
Background:
- Oxycodone pharmacokinetics are established from neonates to adults, with allometry and age-related maturation influencing clearance.
- Target oxycodone concentration for effective analgesia varies with pain intensity, duration, and individual patient factors.
Purpose of the Study:
- To simulate and determine optimal intravenous or parenteral oxycodone loading and maintenance doses for neonates through to obese adults.
- To achieve a target concentration of 35 mcg.L⁻¹ (±20%) associated with adequate analgesia and minimal respiratory depression risk.
Main Methods:
- Pharmacokinetic simulation was employed to estimate oxycodone doses across a wide age range.
- A target concentration of 35 mcg.L⁻¹ was assumed for adequate pain relief and safety.
Main Results:
- 84% of simulated oxycodone concentrations fell within the target range during maintenance dosing.
- Clearance maturation with age reduced concentration variability; neonates exhibited immature clearance.
- Specific intravenous loading and maintenance doses were determined for a 5-year-old child and a typical adult.
Conclusions:
- Simulation-derived loading and maintenance doses aim to achieve a target oxycodone concentration of 35 mcg.L⁻¹.
- While age and weight explain 92% of clearance variability, 16% of concentrations remained outside the target range.
- Context-sensitive half-time is longer in neonates, suggesting a prolonged analgesic effect duration compared to older individuals.
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.
