title: Effects of concurrent intravenous morphine sulfate and naltrexone hydrochloride on end-tidal carbon dioxide.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pfizer Inc, Cary, NC, USA. veeru.goli@pfizer.com.
authors.forename: Veeraindar
authors.initials: V
authors.lastname: Goli
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Webster
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lamson
authors.forename: Jody M
authors.initials: JM
authors.lastname: Cleveland
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Sommerville
authors.forename: Eric
authors.initials: E
authors.lastname: Carter