What are the pharmacokinetics of oxycodone (opioid analgesic)?

Pharmacokinetics of Oxycodone

Oxycodone is an opioid with agonist activity at the mu-, delta-, and kappa-opioid receptors and is available in immediate-release (IR) and extended-release (ER) formulations. Oxycodone has a high oral bioavailability of 60-87% due to lower presystemic and first-pass metabolism compared to other oral opioids, making it an effective option for oral administration. 1

Absorption and Bioavailability

• Oxycodone has high oral bioavailability (60-87%) compared to other oral opioids due to lower presystemic and first-pass metabolism 1
• Food intake enhances the extent of absorption (27% increase in AUC) but delays the time to maximum concentration (Tmax from 1.25 to 2.54 hours) 1
• Immediate-release formulations reach peak plasma concentrations more rapidly than extended-release formulations 2
• Extended-release oxycodone tablets have a bi-exponential absorption profile with a rapid component (t½abs = 37 min) accounting for 38% of the dose and a slow component (t½abs = 6.2 h) accounting for 62% of the dose 2

Distribution

• Following intravenous administration, the volume of distribution (Vss) for oxycodone is 2.6 L/kg 1
• Plasma protein binding of oxycodone at 37°C and pH 7.4 is approximately 45% 1
• Oxycodone has been found in breast milk, which is an important consideration for lactating patients 1

Metabolism

• Oxycodone undergoes extensive hepatic metabolism primarily through two pathways 1:
  • N-demethylation to noroxycodone via CYP3A4 (major pathway)
  • O-demethylation to oxymorphone via CYP2D6 (minor pathway)
• The major circulating metabolite is noroxycodone 1
• Significant interindividual variation exists in oxycodone pharmacokinetics, which may affect clinical response 3

Elimination

• Free and conjugated noroxycodone, free and conjugated oxycodone, and oxymorphone are excreted in human urine 1
• The elimination half-life of oxycodone is approximately 3.5-4 hours for immediate-release formulations 1
• It takes approximately 18-24 hours to reach steady-state plasma concentrations with oxycodone tablets 1

Special Considerations

• Dose proportionality has been established for oxycodone tablets at doses of 5 mg, 15 mg, and 30 mg based on extent of absorption (AUC) 1
• Extended-release formulations maintain effective concentrations for approximately 12 hours, allowing twice-daily dosing 2
• Patients with renal or hepatic impairment may have altered pharmacokinetics and require dose adjustments 3
• CYP2D6 genetic polymorphisms can affect oxycodone metabolism, potentially altering analgesic efficacy 3

Clinical Implications

• Oxycodone provides similar analgesic effects to morphine but with a specific pharmacologic profile and greater analgesic potency 4
• The high oral bioavailability makes oxycodone suitable for oral administration in various pain conditions 5
• When combined with acetaminophen, the acetaminophen dose must be monitored to avoid potential hepatic toxicity 6
• Prolonged-release oxycodone/naloxone formulations have shown effective analgesia with reduced opioid-induced constipation for long-term use in cancer-related pain 6

Common Pitfalls and Caveats

• Oxycodone can cause significant adverse effects including respiratory depression, constipation, and sedation similar to other opioids 5
• Concomitant use of CYP3A4 inhibitors or inducers may significantly alter oxycodone plasma concentrations 1
• Extended-release formulations should not be crushed, chewed, or dissolved as this can lead to rapid release and absorption of a potentially fatal dose 1
• Oxycodone has abuse potential equivalent to morphine and should be prescribed with appropriate caution 5
• Conversion between opioids should be done carefully as equianalgesic doses may vary between individuals 6