Treatment of opioid-induced constipation with oral naloxone: a pilot study.
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.
Culpepper-Morgan
J A
JA
Laboratory of Dr. M. J. Kreek, Rockefeller University, New York, NY 10021.
Inturrisi
C E
CE
Portenoy
R K
RK
Foley
K
K
Houde
R W
RW
Marsh
F
F
Kreek
M J
MJ
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
D009270:Naloxone; D010098:Oxycodone; D008691:Methadone