Pharmacokinetic comparison of intravenous and intranasal administration of oxycodone

For patients with chronic pain, treatment with oral analgesics is considered most convenient and feasible. Sometimes, however, the oral route cannot be used because of difficulties with swallowing, nausea, vomiting and gastrointestinal obstruction. To investigate the applicability of the nasal route for the administration of oxycodone, we studied the intravenous and intranasal pharmacokinetics of oxycodone in healthy volunteers.

Ten healthy volunteers (3 males and 7 females) were given either an intravenous bolus of oxycodone hydrochloride 0.05 mg/kg or nasal sprays of oxycodone hydrochloride 0.1 mg/kg in a cross-over manner. Blood was sampled and subjective effects and side effects were recorded for 10 h.

After intravenous administration of oxycodone, the plasma clearance of oxycodone was 0.83 +/- 0.33 l/min (mean +/- SD) and the volume of distribution at steady-state 2.02 +/- 1.47 l/kg and the terminal elimination half-life 157 +/- 47 min. After intranasal administration, peak plasma concentration of oxycodone was 13 +/- 6 ng/ml and it was reached in the median time of 25 min. The intranasal bioavailability of oxycodone was 0.46 +/- 0.34. No clinically significant changes in blood pressure or heart rate were observed but all subjects experienced somnolence after both modes of administration.

The results of this study show that oxycodone is rapidly and rather effectively absorbed from the nasal mucosa but the interindividual differences are large. The intranasal route may in some cases be an attractive alternative to oral or parenteral administration of opioid analgesics. However, because of large interindividual differences, it is prudent to titrate the dose of intranasal oxycodone individually.