Oxymorphone extended release does not affect CYP2C9 or CYP3A4 metabolic pathways

J Clin Pharmacol. 2005 Mar;45(3):337-45. doi: 10.1177/0091270004271969.

Abstract

Two 14-day, randomized, open-label, parallel-group studies examined the effects of extended-release (ER) oxymorphone on CYP2C9 or CYP3A4 metabolic activities in healthy subjects. On days -1, 7, and 14, subjects received either a CYP2C9 probe (tolbutamide 500 mg) or CYP3A4 probes (midazolam and [14C N-methyl]-erythromycin for the erythromycin breath test). Subjects were randomized to 5 groups: high-dose oxymorphone ER (3 x 20 mg q12h) + naltrexone (50 mg q24h); low-dose oxymorphone ER (10-20 mg q12h); rifampin (2 x 300 mg q24h), an inducer of CYP2C9 and CYP3A4 activities; naltrexone (50 mg q24h); or CYP probes alone (controls). Probe metabolism was significantly altered by rifampin on days 7 and 14 (P < .05), whereas probe metabolism was not significantly affected by low-dose oxymorphone ER or by high-dose oxymorphone ER plus naltrexone. Oxymorphone ER exhibits a minimal potential for causing metabolic drug-drug interactions mediated by CYP2C9 or CYP3A4.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacology*
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism*
  • Delayed-Action Preparations
  • Drug Interactions
  • Erythromycin / administration & dosage
  • Erythromycin / pharmacokinetics
  • Female
  • Humans
  • Male
  • Midazolam / administration & dosage
  • Midazolam / pharmacokinetics
  • Middle Aged
  • Naltrexone / pharmacology
  • Oxymorphone / administration & dosage
  • Oxymorphone / pharmacology*
  • Rifampin / pharmacology
  • Tolbutamide / pharmacokinetics

Substances

  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Naltrexone
  • Erythromycin
  • Cytochrome P-450 Enzyme System
  • Tolbutamide
  • Oxymorphone
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Midazolam
  • Rifampin