Pharmacokinetics and dose-proportionality of oxymorphone extended release and its metabolites: results of a randomized crossover study

Pharmacotherapy. 2004 Apr;24(4):468-76. doi: 10.1592/phco.24.5.468.33347.


Study objective: To evaluate the pharmacokinetics and dose-proportionality of four dose strengths (5, 10, 20, and 40 mg) of oxymorphone extended release (ER) under both single-dose and steady-state conditions.

Design: Randomized, three-period, four-sequence, crossover study.

Setting: Bioavailability clinic.

Subjects: Twenty-four healthy adult volunteers.

Intervention: Each subject received three of the four possible doses. The three 8-day administration periods were separated by a 7-day washout. Plasma was collected for up to 48 hours after a single dose on day 1 and during a 12-hour dosage interval at steady state. Naltrexone was administered to reduce opioid-related adverse effects.

Measurements and main results: Twenty-three subjects completed at least one study period. Dose-proportionality and linearity were confirmed after single doses (mean oxymorphone ER area under the concentration versus time curve [AUC] 4.54, 8.94, 17.80, and 37.90 ng x hr/ml for 5-, 10-, 20-, and 40-mg doses, respectively) and at steady state (mean oxymorphone ER AUC 5.60, 9.77, 19.3, and 37.0 ng x hr/ml for 5-, 10-, 20-, and 40-mg doses every 12 hrs, respectively). Similar results were found for maximum plasma concentration. Metabolite (6-hydroxyoxymorphone and oxymorphone-3-glucuronide) plasma levels also increased in a linear fashion after single-dose administration and at steady state.

Conclusion: The pharmacokinetic profile of oxymorphone ER demonstrates linearity and dose-proportionality under single-dose and steady-state conditions for the parent compound and its metabolites for doses of 5-40 mg.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / blood
  • Analgesics, Opioid / pharmacokinetics*
  • Area Under Curve
  • Biological Availability
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Female
  • Glucuronides / blood
  • Humans
  • Male
  • Middle Aged
  • Oxymorphone / administration & dosage
  • Oxymorphone / analogs & derivatives
  • Oxymorphone / blood
  • Oxymorphone / pharmacokinetics*


  • 4,5-epoxy-3,6,14-trihydroxy-17-methylmorphinan
  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Glucuronides
  • oxymorphone-3-glucuronide
  • Oxymorphone