Naloxone as part of a prolonged release oxycodone/naloxone combination reduces oxycodone-induced slowing of gastrointestinal transit in healthy volunteers.
Summary of "Naloxone as part of a prolonged release oxycodone/naloxone combination reduces oxycodone-induced slowing of gastrointestinal transit in healthy volunteers."
Objectives: This exploratory study in healthy volunteers investigated the effect of single doses of oxycodone on gastrointestinal (GI) transit time and the degree to which a single dose of naloxone reverses the oxycodone-induced effect. Methods: Fifteen healthy male volunteers received: oxycodone 10 and 20 mg, oxycodone/naloxone 10/5 and 20/10 mg (all as prolonged release tablets) and placebo. Each dose was radiolabelled and administered with a capsule containing radiolabelled resin (surrogate for GI contents). Results: Scintigraphic analysis showed that 20 mg oxycodone significantly increased colon arrival time (mean 7.19 vs 5.15 h for placebo, p = 0.0159). Mean colon arrival time for oxycodone/naloxone 20/10 mg (5.16 h) was similar to placebo, although the difference between oxycodone/naloxone 20/10 mg versus oxycodone 20 mg was not significant (p = 0.0653). Colonic geometric centre analysis showed a significant increase in mean time for the resin to reach the colon following oxycodone 10 and 20 mg compared with placebo (increases of 5.3 and 8.8 h). There was no significant effect of naloxone at the lower dose; however, oxycodone/naloxone 20/10 mg significantly reduced mean colonic transit time by 2.1 h (p = 0.0376). Conclusion: A single dose of oxycodone 20 mg significantly prolonged GI transit time but this effect was reduced by co-administration of naloxone.
Affiliation
Mundipharma Research Ltd, Cambridge Science Park, Milton Road, Cambridge, CB4 0GW, UK +44 0 1223 424444 ; +44 0 1223 425794 ; kevin.smith@mundipharma-rd.eu.
Journal Details
This article was published in the following journal.
Name: Expert opinion on investigational drugs
ISSN: 1744-7658
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21395483
- DOI: http://dx.doi.org/10.1517/13543784.2011.563236
Medical and Biotech [MESH] Definitions
Naltrexone
Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.
Naloxone
A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.
Thiorphan
A potent inhibitor of membrane metalloendopeptidase (ENKEPHALINASE). Thiorphan potentiates morphine-induced ANALGESIA and attenuates naloxone-precipitated withdrawal symptoms.
Diprenorphine
A narcotic antagonist similar in action to NALOXONE. It is used to remobilize animals after ETORPHINE neuroleptanalgesia and is considered a specific antagonist to etorphine.
D-ala(2),mephe(4),met(0)-ol-enkephalin
A stable synthetic analog of methionine enkephalin (ENKEPHALIN, METHIONINE). Actions are similar to those of methionine enkephalin. Its effects can be reversed by narcotic antagonists such as naloxone.
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