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


METHODS
Randomized, three-period, four-sequence, crossover study.


METHODS
Bioavailability clinic.


METHODS
Twenty-four healthy adult volunteers.


METHODS
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.


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.


CONCLUSIONS
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.
Adams
Michael P
MP
SFBC New Drug Services, Kennett Square, Pennsylvania 19348-2412, USA. mpadams@newdrugservices.com
Ahdieh
Harry
H
D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005260:Female; D020719:Glucuronides / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D010111:Oxymorphone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*
C488458:4,5-epoxy-3,6,14-trihydroxy-17-methylmorphinan; D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D020719:Glucuronides; C488459:oxymorphone-3-glucuronide; D010111:Oxymorphone