Single-dose and steady-state pharmacokinetics of MoxDuo™, a dual-opioid formulation containing a fixed-ratio of morphine and oxycodone

Abstract

Concomitant administration of opioids has been shown to enhance analgesia with fewer AEs compared with a single opioid in both animal and human studies. These observations warrant further investigation of coadministered opioids in the management of pain. This 6-day study assessed single-dose and steady-state pharmacokinetics of morphine and oxycodone following oral administration of fixed-ratio, dual-opioid capsules (Q8003 [MoxDuo™]; 3:2 morphine:oxycodone) in 18 healthy men and women. A single-dose, 2-way crossover design was utilized to compare the pharmacokinetics of Q8003 following administration on Days 1 and 3 of either low-strength (3/2 mg) or high-strength (12/8 mg) capsules. Pharmacokinetic parameters following multiple-dose administration of high-dose Q8003 every 4 hours during Days 4 to 6 were also examined. Subjects received naltrexone 50 mg approximately 12 hours and 30 minutes before each Q8003 dose. Mean plasma concentrations during the elimination phase for morphine and the morphine metabolites declined at similar rates for the 3/2-mg dose, resulting in apparent parallel profiles. Similar parallel profiles were observed for the 12/8-mg dose. Mean plasma levels of oxycodone also appeared to decline in a parallel manner for the 3/2-mg capsule and the 12/8-mg capsule. Steady-state conditions for all analytes were reached prior to Day 6. This was evidenced by analysis of the 4-hour dosing intervals during this period, which showed similar predose and 4-hour plasma concentrations. Oral doses of Q8003 were well-tolerated, with 7 subjects (38.9%) experiencing 13 treatment-emergent AEs; none were considered serious. Results from this study demonstrate that mean plasma concentrations of morphine, morphine metabolites, and oxycodone decline in a parallel manner, respectively, following single-dose administration of Q8003 3/2 mg or 12/8 mg. Results also show that morphine and oxycodone achieve steady-state plasma conditions within 48 hours of Q8003 administration. (Supported by QRxPharma, Bedminster, NJ.)