Effects of concurrent intravenous morphine sulfate and naltrexone hydrochloride on end-tidal carbon dioxide

• Published in: Harm reduction journal Vol. 9; no. 1; p. 13
• Main Authors: Goli, Veeraindar, Webster, Lynn R, Lamson, Michael J, Cleveland, Jody M, Sommerville, Kenneth W, Carter, Eric
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 15.03.2012; BioMed Central; BMC
• Subjects: Analysis; Capnography; Carbon dioxide; Dosage and administration; Drug abuse; Drug overdose; Harm reduction; Metabolic disorders; Morphine; Naltrexone; Opioid; Opioid antagonist; Opioid overdose; Overdose; Pain management; Pharmaceutical industry; Respiratory depression; Sulfates; United States > US
• ISSN: 1477-7517; 1477-7517
• DOI: 10.1186/1477-7517-9-13

Respiratory depression, a potentially fatal side-effect of opioid-overdose, may be reversed by timely administration of an opioid antagonist, such as naloxone or naltrexone. Tampering with a formulation of morphine sulfate and sequestered naltrexone hydrochloride extended release capsules (MS-sNT) releases both the opioid morphine and the antagonist naltrexone. A study in recreational opioid-users indicated that morphine and naltrexone injected in the 25:1 ratio (duplicating the ratio of the formulation) found MS-sNT reduced morphine-induced euphoric effects vs intravenous (IV) morphine alone. In the same study, the effects of morphine + naltrexone on end-tidal carbon dioxide (EtCO2), a measure of respiratory-depression, were evaluated and these data are reported here. Single-center, placebo-controlled, double-blind crossover study. Non-dependent male opioid users were randomized to receive single IV doses of placebo, 30 mg morphine alone, and 30 mg morphine + 1.2 mg naltrexone. EtCO2 was measured by noninvasive capnography. Significant differences in EtCO2 least-squares means across all treatments for maximal effect (Emax) and area under the effect curve (AUE0-2, AUE0-8, AUE0-24) were detected (all p ≤ 0.0011). EtCO2 Emax values for morphine + naltrexone were significantly reduced vs morphine alone (42.9 mm Hg vs 47.1 mm Hg, p < 0.0001) and were not significantly different vs placebo (41.9 mm Hg). Median time to reach maximal effect (TEmax) was delayed for morphine + naltrexone vs morphine alone (5.0 h vs 1.0 h). Results provide preliminary evidence that the naltrexone:morphine ratio within MS-sNT is sufficient to significantly reduce EtCO2 when administered intravenously to non-dependent male recreational opioid-users. Further studies with multiple measures of respiratory-function are warranted to determine if risk of respiratory depression is also reduced by naltrexone in the tampered formulation.