Does the pharmacology of oxycodone justify its increasing use as an analgesic?

Oxycodone is a semisynthetic opioid analgesic that is increasingly used for the treatment of acute, cancer, and chronic non-malignant pain. Oxycodone was synthesized in 1917 but its pharmacological properties were not thoroughly studied until recently. Oxycodone is a fairly selective μ-opioid receptor agonist, but there is a striking discrepancy between the relatively low binding potential and G protein activation by oxycodone and its analgesic efficacy. It has been claimed that this is because of active metabolites and enhanced passage to the central nervous system by active transport. We critically review studies on the basic pharmacology of oxycodone and on its pharmacokinetics and pharmacodynamics in humans. In particular, the role of pharmacogenomics and population pharmacokinetics in understanding the properties of oxycodone is discussed in detail. We compare oxycodone with morphine, the standard opioid in clinical use.

► Oxycodone has a rapid onset of action, probably because of its higher permeability across the blood–brain barrier and cerebral accumulation.
► The mechanism for cerebral accumulation of oxycodone is unknown.
► Oxycodone is metabolized by CYP enzymes, making it more prone to drug interactions than morphine.