COMPARATIVE OXYCODONE PHARMACOKINETICS IN HUMANS AFTER INTRAVENOUS, ORAL, AND RECTAL ADMINISTRATION

The pharmacokinetics of oxycodone have been determined after single-dose administration by the intravenous (4.6-7.3 mg), oral (tablets, 9.1 mg and syrup, 9.1 mg), and rectal (30 mg) routes, in 48 patients undergoing minor surgery. There were no significant differences in the mean elimination half-lives between the intravenous (5.45 +/- 1.43 h), oral tablets (5.65 +/- 1.13 h), oral syrup (4.80 +/- 1.13 h), and rectal suppository (5.40 +/- 1.19 h) formulations of oxycodone. After intravenous administration, the mean plasma clearance of oxycodone was 25.5 +/- 10.1 L/h and the mean volume of distribution at steady state was 2.5 +/- 0.8 L/kg. The mean normalized area under the curve (AUC/D) obtained after intravenous dosing (48.2 +/- 30.2 mug . h/L/mg) was more than twice the AUC/D values obtained after the administration of oxycodone tablets (19.8 +/- 3.5 mug . h/L/mg), oxycodone syrup (17.5 +/- 5.3 mug . h/L/mg), and rectal suppository (20.3 +/- 5.1 mug - h/L/mg), indicating that the amount of oxycodone reaching the systemic circulation after the extravascular routes of administration was <50% of that obtained after intravenous dosing. The mean absorption lag times after oxycodone tablets (0.52 +/- 0.33 h), oxycodone syrup (0.48 +/-0.40 h), and rectal suppository (0.76 +/- 0.47 h) were consistent with the onset of pharmacological effects reported by the patients.