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
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Analgesics, Opioid / administration & dosage
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Analgesics, Opioid / pharmacology*
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Aryl Hydrocarbon Hydroxylases / metabolism*
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Cytochrome P-450 CYP2C9
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Cytochrome P-450 CYP3A
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Cytochrome P-450 Enzyme System / metabolism*
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Delayed-Action Preparations
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Drug Interactions
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Erythromycin / administration & dosage
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Erythromycin / pharmacokinetics
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Female
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Humans
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Male
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Midazolam / administration & dosage
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Midazolam / pharmacokinetics
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Middle Aged
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Naltrexone / pharmacology
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Oxymorphone / administration & dosage
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Oxymorphone / pharmacology*
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Rifampin / pharmacology
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Tolbutamide / pharmacokinetics
Substances
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Analgesics, Opioid
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Delayed-Action Preparations
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Naltrexone
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Erythromycin
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Cytochrome P-450 Enzyme System
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Tolbutamide
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Oxymorphone
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CYP2C9 protein, human
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Cytochrome P-450 CYP2C9
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Aryl Hydrocarbon Hydroxylases
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CYP3A protein, human
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Cytochrome P-450 CYP3A
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CYP3A4 protein, human
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Midazolam
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Rifampin