Abuse quotient of orally administered mnk-795 extended-release oxycodone/acetaminophen tablets vs immediate-release oxycodone/ acetaminophen tablets in recreational users of prescription opioids

Objective: To compare the abuse quotient, which is the ratio between the maximum plasma concentration (Cmax) and the time to reach Cmax (tmax), of MNK-795 extended-release oxycodone/acetaminophen (ER OC/APAP), immediate-release (IR) OC/APAP, and placebo. Design: A randomized, double-blind, double-dummy, active- and placebo-controlled crossover study. Setting: Contract research organization clinic. Participants: Healthy, nondependent recreational opioid users, with institutional review board approval and informed consent; n=61. Interventions: During each treatment period, subjects received 1 of 7 treatments in randomized order: lower-dose ER OC/APAP (15 mg OC/650 mg APAP), higher-dose ER OC/APAP (30 mg OC/ 1300 mg APAP), lower-dose IR OC/APAP (15 mg OC/650 mg APAP), higher-dose IR OC/APAP (30 mg OC/1300 mg APAP), crushed higher-dose ER OC/APAP, crushed higher-dose IR OC/ APAP, or placebo. Main Outcome Measures: Predose and 0-12 hours postdose for each treatment, measurements were obtained for validated scales of pharmacodynamic (PD) subjective effects (eg, drug liking, drug high, and good drug effects) and pharmacokinetic parameters including the abuse quotient (AQ; peak concentration/ time to peak concentration [Cmax/tmax]). All adverse events were recorded. Results or Clinical Course: The mean AQ was lower for both low-dose (4.77) and high-dose (11.83) ER OC/APAP than low-dose (27.27) or high-dose (52.50) IR OC/APAP. The AQ correlated significantly (P<0.0001) with the Emax (peak PD effect) for drug liking (R2=0.8716), drug high (R2=0.8869), and good drug effects (R2=0.8874). For all participant-reported effects, Emax correlated more strongly with Cmax than with AQ. Conclusions: The AQ was strongly correlated with validated PD measures of subjective drug effects that have been associated with abuse and suggests that ER OC/APAP has lower liability for abuse than IR OC/APAP.