title: Treatment of opioid-induced constipation with oral naloxone: a pilot study.
abstract: 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.
authors.affiliation: Laboratory of Dr. M. J. Kreek, Rockefeller University, New York, NY 10021.
authors.forename: J A
authors.initials: JA
authors.lastname: Culpepper-Morgan
authors.forename: C E
authors.initials: CE
authors.lastname: Inturrisi
authors.forename: R K
authors.initials: RK
authors.lastname: Portenoy
authors.forename: K
authors.initials: K
authors.lastname: Foley
authors.forename: R W
authors.initials: RW
authors.lastname: Houde
authors.forename: F
authors.initials: F
authors.lastname: Marsh
authors.forename: M J
authors.initials: MJ
authors.lastname: Kreek
mesh_terms: D000328:Adult; D003248:Constipation / Q000139:chemically induced* / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008691:Methadone / Q000009:adverse effects*; D008875:Middle Aged; D009270:Naloxone / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010098:Oxycodone / Q000009:adverse effects*; D010865:Pilot Projects; D019966:Substance-Related Disorders
chemical_list: D009270:Naloxone; D010098:Oxycodone; D008691:Methadone