PHARMACOKINETIC COMPARISON OF INTRAVENOUS AND INTRANASAL ADMINISTRATION OF OXYCODONE

Background: For patients with chronic pain, treatment with oral analge sics is considered most convenient and feasible. Sometimes, however, t he 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 oxycodon e in healthy volunteers. Methods: Ten healthy volunteers (3 males and 7 females) were given either an intravenous bolus of oxycodone hydroch loride 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. Results: After intravenous admini stration 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 ii kg and the terminal elimination half-life 157+/-47 min. After intranasal administration, peak plasma concentration of oxycodon e was 13+/-6 ng/ml and it was reached in the median time of 25 min. Th e intranasal bioavailability of oxycodone was 0.46+/-0.34. No clinical ly significant changes in blood pressure or heart rate were observed b ut all subjects experienced somnolence after both modes of administrat ion. Conclusions: The results of this study show that oxycodone is rap idly and rather effectively absorbed from the nasal mucosa but the int erindividual differences are large. The intranasal route may in some c ases be an attractive alternative to oral or parenteral administration of opioid analgesics. However, because of large interindividual diffe rences, it is prudent to titrate the dose of intranasal oxycodone indi vidually. (C) Acta Anaesthesiologica Scandinavica 41 (1997).