Abstract
BACKGROUND: Abuse of prescription opioids, particularly by intravenous (IV) administration, can cause respiratory depression and death. ALO-02, an abuse-deterrent opioid formulation, is designed to release sequestered naltrexone upon manipulation by crushing, thereby antagonizing the pharmacologic effects of oxycodone. This exploratory post-hoc analysis examined the effects of IV administration of simulated crushed ALO-02 on end-tidal carbon dioxide (EtCO(2)), a surrogate marker of respiratory depression. METHODS: Data were obtained from a randomized, double-blind, placebo-controlled, three-way crossover study in nondependent recreational opioid users that evaluated the abuse potential of IV administered oxycodone 20 mg + naltrexone 2.4 mg (simulating crushed ALO-02) versus oxycodone 20 mg or placebo. EtCO(2) was measured as a secondary endpoint using noninvasive capnography at baseline and postdose intervals, up to 24 h. RESULTS: Baseline EtCO(2) (mean ± standard error of the mean (SEM)) values (n = 33) were similar across treatments: 33.5 ± 0.9, 33.5 ± 0.8, and 34.0 ± 0.7 mmHg for oxycodone 20 mg + naltrexone 2.4 mg, oxycodone 20 mg, and placebo, respectively. After dosing, mean ± SEM of the maximum effect (E(max)) on EtCO(2) was 37.5 ± 0.6, 40.5 ± 0.8, and 36.9 ± 0.6 mmHg for oxycodone 20 mg + naltrexone 2.4 mg, oxycodone 20 mg, and placebo, respectively. E(max) values were significantly lower for oxycodone 20 mg + naltrexone 2.4 mg versus oxycodone 20 mg (p = 0.0005), and not different from placebo (p > 0.05). CONCLUSIONS: This abuse-potential study suggests that naltrexone released from ALO-02 tampering by crushing attenuates oxycodone-induced increase of EtCO(2) in nondependent recreational opioid users.