Oxycodone clearance is markedly reduced with advancing age: a population pharmacokinetic study

Area of Science:

• Pharmacology
• Geriatric Medicine
• Clinical Pharmacy

Background:

• Oxycodone, a widely used µ-opioid receptor agonist, has seen increased global utilization.
• Limited pharmacokinetic data exists for oxycodone in elderly populations.
• Population pharmacokinetic data for oxycodone is scarce.

Purpose of the Study:

• To investigate the population pharmacokinetics of oxycodone.
• To identify factors influencing oxycodone pharmacokinetics, particularly in the elderly.

Main Methods:

• Analysis of 1272 plasma oxycodone samples from 77 individuals (aged 19-89).
• Utilized non-linear mixed-effects modeling to estimate pharmacokinetic parameters.
• Assessed inter- and intra-individual variability and covariate effects through simulations.

Main Results:

• A two-compartment linear model best described the data.
• Lean body mass and age were significant covariates for elimination clearance and central compartment volume.
• Elimination half-life and context-sensitive half-time increased with age, with elderly showing a 20% higher oxycodone concentration.

Conclusions:

• Age is a significant covariate affecting oxycodone pharmacokinetics.
• Reduced and carefully titrated oxycodone dosing is recommended for elderly patients.
• This approach aims to prevent oxycodone accumulation and associated hazardous side effects.