Treatment of opioid-induced constipation with oral naloxone: A pilot study

Culpepper-Morgan, Joan; Inturrisi, Charles E.; Portenoy, Russell K.; Foley, Kathleen M.; Houde, Raymond W.; Marsh, Franklin; Kreek, Mary Jeanne

doi:10.1038/clpt.1992.106

Cited by 196 publications

(98 citation statements)

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“…However, as was replicated in the present study, during long-term stabilization in methadone maintenance, with cessation of illicit drug use, and with the accompanying decreasing preoccupation with illicit drug use seen clinically, responsivity to metyrapone administration normalizes. Furthermore, abstinence from opioids in dependent individuals is associated with HPA axis activation, which has been demonstrated to occur concomitantly (Rosen et al 1996) or even precede subjective symptoms of withdrawal (Culpepper-Morgan et al 1992, Culpepper-Morgan and.…”

Section: Discussionmentioning

confidence: 99%

Altered HPA Axis Responsivity to Metyrapone Testing in Methadone Maintained Former Heroin Addicts with Ongoing Cocaine Addiction

Schluger

Borg

et al. 2001

Neuropsychopharmacology

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Section: Discussionmentioning

confidence: 99%

Altered HPA Axis Responsivity to Metyrapone Testing in Methadone Maintained Former Heroin Addicts with Ongoing Cocaine Addiction

Schluger

Borg

et al. 2001

Neuropsychopharmacology

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“…Selective antagonism of opioid-induced side effects by tertiary compounds such as naloxone or nalmephene have been attempted. Success has been limited by the propensity for these compounds to reverse analgesia or to induce opioid withdrawal (Gowan et al, 1988;Sykes, 1991;Culpepper-Morgan et al, 1992;Cheskin et al, 1995).…”

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confidence: 99%

Effects of Subcutaneous Methylnaltrexone on Morphine-Induced Peripherally Mediated Side Effects: A Double-Blind Randomized Placebo-Controlled Trial

Yuan¹,

Wei²,

Foss³

et al. 2002

J Pharmacol Exp Ther

111

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Methylnaltrexone, the first peripheral opioid receptor antagonist, has the potential to prevent or reverse opioid-induced peripherally mediated side effects without affecting analgesia. In previous human trials, we demonstrated that intravenous methylnaltrexone prevented morphine-induced delay in gastrointestinal transit time. We also observed that the compound decreased some of the morphine-induced troublesome subjective effects. However, the effects of subcutaneous methylnaltrexone, a more convenient route of administration, have not been evaluated. In this controlled trial, we evaluated the efficacy of subcutanous methylnaltrexone in antagonizing morphine-induced delay in oral-cecal transit time. In addition, opioid-induced unpleasant subjective effects and pharmacokinetics were studied. We observed that in the first group (n ϭ 6) morphine (0.05 mg/kg intravenously) increased the transit time from a baseline level of 85 Ϯ 20.5 min to 155 Ϯ 27.9 min (mean Ϯ S.D., P Ͻ 0.01). After 0.1 mg/kg subcutaneous methylnaltrexone plus morphine, the transit time reduced to 110 Ϯ 41.0 min. In the second group (n ϭ 6), morphine increased the transit time from a baseline level of 98 Ϯ 49.1 min to 140 Ϯ 58.2 min (P Ͻ 0.01). After 0.3 mg/kg subcutaneous methylnaltrexone plus morphine, the transit time reduced to 108 Ϯ 59.6 min (P Ͻ 0.05 compared with placebo plus morphine). In addition, subcutaneous methylnaltrexone significantly decreased morphineinduced subjective rating changes. Pharmacokinetic data after subcutaneous drug injection were compared to the data obtained from previous intravenous and oral administrations. Our results suggest that subcutaneous methylnaltrexone may have clinical utility in treating opioid-induced constipation and reducing opioid-induced unpleasant subjective symptoms.

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“…24,25 While there is some evidence that prototypical μ opioid receptor antagonists, such as naltrexone and naloxone, attenuate POI and chronic opioid-induced bowel dysfunction (OBD), [26][27][28] their clinical value in these GI disorders is limited given that these drugs cross the blood brain barrier readily, and thus can attenuate opioid-induced analgesia and provoke an opioid behavioral withdrawal syndrome. 28,29 However, it is noteworthy that Targin ® , a combination of oxycodone and naloxone, is effi cacious in the treatment of moderate to severe pain without signifi cant constipation; 30,31 its value in POI therapy remains to be determined.…”

Section: Mechanism Of Action Of Alvimopanmentioning

confidence: 99%

Safety and efficacy update: Alvimopan in postoperative ileus

Beattie

2009

Clinical Medicine. Therapeutics

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Postoperative ileus (POI) in patients undergoing abdominal surgery is associated with signifi cant morbidity. In 2008, alvimopan (Entereg ® ) was approved by the Food and Drug Administration (FDA), and is the only available POI therapy in the United States for patients undergoing bowel resection. Data from preclinical studies demonstrate that alvimopan and its primary metabolite, ADL 08-0011, behave as potent μ opioid receptor antagonists. In animals, alvimopan and ADL 08-0011 attenuate opioid agonist-induced reductions in gastrointestinal (GI) transit. Higher doses of alvimopan are required to inhibit opioid-induced analgesia as a result of its inability to penetrate the central nervous system (CNS). ADL 08-0011 is also peripherally selective, although to a lesser degree than alvimopan. In multiple species, including humans, alvimopan has low oral bioavailability, while ADL 08-0011, following its generation by human gut microfl ora, is more readily absorbed and achieves higher exposures. Three Phase 2 and fi ve Phase 3 clinical trials have been conducted to investigate the effi cacy and tolerability of alvimopan in patients undergoing bowel resection. An additional Phase 3 study was conducted in hysterectomy patients. In the majority of the studies, statistically signifi cant, and clinically meaningful, acceleration of GI recovery has been demonstrated. Consistent with animal data, alvimopan has no effect on opioid agonist-induced analgesia in healthy human subjects and POI patients. Clinical experience to date in POI patients indicates that alvimopan is well tolerated when used according to its approved dosing regimen (12 mg b.i.d. for up to 7 days). In this article, the preclinical and clinical properties of alvimopan are reviewed.

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Treatment of opioid-induced constipation with oral naloxone: A pilot study

Cited by 196 publications

References 0 publications

Altered HPA Axis Responsivity to Metyrapone Testing in Methadone Maintained Former Heroin Addicts with Ongoing Cocaine Addiction

Altered HPA Axis Responsivity to Metyrapone Testing in Methadone Maintained Former Heroin Addicts with Ongoing Cocaine Addiction

Effects of Subcutaneous Methylnaltrexone on Morphine-Induced Peripherally Mediated Side Effects: A Double-Blind Randomized Placebo-Controlled Trial

Safety and efficacy update: Alvimopan in postoperative ileus

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