Long-term administration may be associated with less toxicity in comparison with morphine. The clinical efficacy of oxycodone is similar to that of morphine, with a ratio of 1/1.5-2 for the treatment of cancer pain. These mechanisms also play a part in the onset of dependence and tolerance. Oxycodone has the same mechanism of action as other opioids: binding to a receptor, inhibition of adenylyl-cyclase and hyperpolarisation of neurons, and decreased excitability. Oxycodone metabolism is more predictable than that of morphine, and therefore titration is easier. The two main metabolites are oxymorphone-which is also a very potent analgesic-and noroxycodone, a weak analgesic.
Most of the drug is metabolised in the liver, while the rest is excreted by the kidney along with its metabolites. Oral bioavailability ranges from 60 to 87%, and plasma protein binding is 45%. Plasma halflife is 3-5 h (half that of morphine) and stable plasma levels are reached within 24 h (2-7 days for morphine). Its effect commences one hour after administration and lasts for 12 h in the controlled-release formulation. Equivalence with regard to morphine is 1:2. Oxycodone is a semi-synthetic opioid with an agonist activity on mu, kappa and delta receptors.
