Oxymorphone extended release does not affect CYP2C9 or CYP3A4 metabolic pathways

• Published in: Journal of clinical pharmacology Vol. 45; no. 3; p. 337
• Main Authors: Adams, Michael, Pieniaszek, Jr, Henry J, Gammaitoni, Arnold R, Ahdieh, Harry
• Format: Journal Article
• Language: English
• Published: England 01.03.2005
• Subjects: 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
• ISSN: 0091-2700
• DOI: 10.1177/0091270004271969

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.