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

• Published in: Clinical pharmacology and therapeutics Vol. 52; no. 1; p. 90
• Main Authors: Culpepper-Morgan, J A, Inturrisi, C E, Portenoy, R K, Foley, K, Houde, R W, Marsh, F, Kreek, M J
• Format: Journal Article
• Language: English
• Published: United States 01.07.1992
• Subjects: Adult; Constipation - chemically induced; Constipation - drug therapy; Dose-Response Relationship, Drug; Female; Humans; Male; Methadone - adverse effects; Middle Aged; Naloxone - blood; Naloxone - pharmacokinetics; Naloxone - therapeutic use; Oxycodone - adverse effects; Pilot Projects; Substance-Related Disorders
• ISSN: 0009-9236
• DOI: 10.1038/clpt.1992.106

Opioids cause constipation by binding to specific opioid receptors in the enteric and central nervous systems. First-pass glucuronidation limits systemic bioavailability of oral naloxone. This study was designed to determine if oral naloxone could reverse opioid-induced constipation without precipitating abstinence or recrudescence of pain in opioid-dependent individuals. Concentrations of unmetabolized and total naloxone, including naloxone glucuronide, were measured by radioimmunoassay. A dose-related increase in symptoms of laxation resulted in all three opioid-dependent patients studied that paralleled the increase in active and total naloxone plasma levels. Withdrawal symptoms occurred with plasma naloxone area under the plasma concentration-time curves above 550 ng.min/ml and with dosing intervals less than 3 hours. Peak plasma levels did not predict withdrawal. Oral naloxone ameliorates opioid-induced constipation in opioid-dependent persons. Titration of dose to a maximum of 12 mg at least 6 hours apart may be needed to avoid adverse reactions.