Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties

Pharmacotherapeutic group: Natural opium alkaloids
ATC code: N02A A05

Oxycodone is a full opioid agonist with no antagonist properties. It has an affinity for kappa, mu and delta opiate receptors in the brain and spinal cord. The therapeutic effect is mainly analgesic, anxiolytic and sedative.

Gastrointestinal System
Opioids may induce spasm of the sphincter of Oddi.

Endocrine System
See section 4.4.
Other pharmacological effects
In- vitro and animal studies indicate various effects of natural opioids, such as morphine, on components of the immune system; the clinical significance of these findings is unknown. Whether oxycodone, a semisynthetic opioid, has immunological effects similar to morphine is unknown.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

Absorption
Mean peak plasma concentrations of approximately 20 ng/ml were achieved within 1.5 hours of administration, median tmax values from two strengths (1 mg/ ml and 10 mg/ml) of liquid being less than 1 hour.

A pharmacokinetic study in healthy volunteers has demonstrated that, following administration of a single 10 mg dose, liquid 1 mg/ml and syrup 10 mg/ml provided an equivalent rate and extent of absorption of oxycodone.

Distribution
Following absorption, oxycodone is distributed throughout the entire body. Approximately 45% is bound to plasma protein.

Metabolism
Oxycodone is metabolised in the liver via CYP3A4 and CYP2D6 to noroxycodone, oxymorphone and noroxymorphone, which are subsequently glucuronidated. Noroxycodone and noroxymorphone are the major circulating metabolites. Noroxycodone is a weak mu opioid agonist.
Noroxymorphone is a potent mu opioid agonist; however, it does not cross the blood-brain barrier to a significant extent. Oxymorphone is a potent mu opioid agonist but is present at very low concentrations following oxycodone administration. None of these metabolites are thought to contribute significantly to the analgesic effect of oxycodone.

Elimination
Oxycodone has an elimination half life of approximately 3-4 hours. The active drug and its metabolites are excreted in urine.

Studies involving controlled release oxycodone have demonstrated that the oral bioavailability of oxycodone is only slightly increased (16%) in the elderly. In patients with renal and hepatic impairment, the bioavailability of oxycodone was increased by 60% and 90%, respectively, and a reduced initial dose is recommended in these groups.