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American Society for Action on Pain
AU - Culpepper-Morgan JA

AU - Inturrisi CE

AU - Portenoy RK

AU - Foley K

AU - Houde RW

AU - Marsh F

AU - Kreek MJ

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

AB - 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.

SO - Clin Pharmacol Ther 1992;52:90-9