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.
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Authors | J A Culpepper-Morgan, C E Inturrisi, R K Portenoy, K Foley, R W Houde, F Marsh, M J Kreek |
Journal | Clinical pharmacology and therapeutics
(Clin Pharmacol Ther)
Vol. 52
Issue 1
Pg. 90-5
(Jul 1992)
ISSN: 0009-9236 [Print] United States |
PMID | 1623695
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Naloxone
- Oxycodone
- Methadone
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Topics |
- Adult
- Constipation
(chemically induced, drug therapy)
- Dose-Response Relationship, Drug
- Female
- Humans
- Male
- Methadone
(adverse effects)
- Middle Aged
- Naloxone
(blood, pharmacokinetics, therapeutic use)
- Oxycodone
(adverse effects)
- Pilot Projects
- Substance-Related Disorders
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