Population pharmacokinetics of oxycodone: Premature neonates to adults.
This is a pooled data study to describe oxycodone pharmacokinetics in premature neonates to adults, when administered via intravenous, nasogastric, buccal and epidural routes. The study also assessed the impact of body composition on oxycodone pharmacokinetics.
Pooled data from four studies to assess oxycodone pharmacokinetics following surgical procedures. Plasma concentration data were collected following administration of 0.1mg/kg oxycodone IV in subjects aged 24 weeks postmenstrual age to 75 years plus a study of epidural oxycodone in adults. In total there were 1317 drug concentrations from 237 individuals, which were combined to form a single three-compartment oxycodone pharmacokinetic analysis.
Patient size (total body weight was the most suitable size scaler) and age were the main predictors of oxycodone clearance, which matured throughout infancy. 8% of the typical adult clearance was reached at 24 weeks post-menstrual age, 33% at term, and 90% at 1 year of age, suggesting that ‘maturation of clearance aligns with the development of metabolic pathways responsible for drug elimination’. Bioavailability was 67% after nasogastric administration, and 99% after buccal administration.
Comments / Take Home Message:
Oxycodone is a semi-synthetic opioid used in the treatment of acute and chronic pain in children and adults. Metabolism pathways are immature in neonates and drug clearance pharmacokinetics increase in a non-linear manner with total body weight.
This analysis provides pharmacokinetic information that can be used to estimate age-dependent dose for children in order to achieve an oxycodone target concentration, while avoiding adverse effects such as respiratory depression.
Reviewed by Dr Jessica Gillett