Oxymorphone Extended Release Does Not Affect CYP2C9 or CYP3A4 Metabolic Pathways

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.

Simulation of Clinical Drug-Drug Interactions from Hepatocyte CYP3A4 Induction Data and Its Potential Utility in Trial Designs

“…B, dose of RIF, 600 mg q.d. The observed DDI data were the means of 9 or 10 subjects (Backman et al, 1996(Backman et al, , 1998Kharasch et al, 2004) for RIF dosed for 5 days, 8 subjects (Link et al, 2008) for RIF dosed for 6 days, 14 subjects (Gorski et al, 2003) for RIF dosed for 7 days, 19 subjects (Chung et al, 2006) for RIF dosed for 9 days, 16 subjects (Adams et al, 2005) for RIF dosed for 14 days, and 57 subjects (Floyd et al, 2003) (Fig. 3, A-C).…”

Oxymorphone: a review

“…Oxymorphone (oxymorphone hydrochloride) (14-hydroxydihydromorphinone), a semisynthetic μ-opioid agonist, was first approved by the US Food and Drug Administration (FDA) in 1959. Oxymorphone has a greater analgesic potency than morphine and, until recently, has been available only as parenteral injection and in suppository form [5]. Recently, an immediate-release (IR) and a long-acting oral formulation of this drug were developed that make oxymorphone a new option for treating moderate to severe pain.…”

Pharmacotherapy for Chronic Low Back Pain

“…The majority of opioids are metabolized by the cytochrome P450 system and have potential for pharmacokinetic interaction with many drugs (Smith, 2009). Exceptions to this are morphine (Coffman et al, 1997), oxymorphone (Adams et al, 2005 metabolism by glucuronidation. Selection of an opioid that is not metabolized via cytochrome P450 enzymes is important when there is a known cytochrome P450 pharmacokinetic interaction with a concurrent medication but may also be desirable in patients likely to be prescribed multiple medications, such as the elderly, patients with psychiatric illness, and patients with multiple medical problems (Smith & Bruckenthal, 2010).…”