Oxymorphone extended release does not affect CYP2C9 or CYP3A4 metabolic pathways.
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.
Adams
Michael
M
SFBC-New Drug Services Inc, Kennett Square, Pennsylvania, USA.
Pieniaszek
Henry J
HJ
Gammaitoni
Arnold R
AR
Ahdieh
Harry
H
D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D065729:Cytochrome P-450 CYP2C9; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D004917:Erythromycin / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000493:pharmacokinetics; D008875:Middle Aged; D009271:Naltrexone / Q000494:pharmacology; D010111:Oxymorphone / Q000008:administration & dosage / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology; D014044:Tolbutamide / Q000493:pharmacokinetics
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D009271:Naltrexone; D004917:Erythromycin; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; D010111:Oxymorphone; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D008874:Midazolam; D012293:Rifampin