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  • 1
    ISSN: 1432-1041
    Keywords: Codeine ; Morphine ; analgesic effect ; plasma concentration ; oral administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A double blind randomised cross over investigation was carried out in 25 male patients undergoing two oral surgical extractions, one for each lower wisdom tooth. The two extractions were performed about 6 weeks apart and were carried out under local anaesthesia. One hour after each extraction the patients randomly received 90 or 45 mg codeine. During the following 5 h the patients rated the intensity of their pain on a visual analogue scale. Blood was simultaneously sampled and assayed for codeine and its metabolite morphine. Mean pain intensity difference was just significantly higher after 90 mg codeine compared to 45 mg. The mean plasma concentrations of codeine and morphine were significantly higher after the 90 mg dose. However, for the two dose levels of codeine there was no obvious relationship between the difference in analgesic effect and the difference in the plasma concentration of codeine or morphine. The plasma concentrations of morphine were 2–3% of those of codeine and the levels were relatively low. Local formation of morphine from codeine within the human brain should therefore be investigated. Four patients were unable to demethylate codeine to a detectable plasma concentration of morphine after 90 mg codeine. In those patients the analgesic effect during the first hours was better after 90 mg codeine than after 45 mg. This suggests some analgesic effect of codeine itself.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: codeine ; morphine ; pharmacokinetics ; steady-state ; oral administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of codeine and its demethylated metabolite, morphine, were determined after single and repeated oral administration of codeine. Twelve healthy volunteers received two doses of codeine 60 mg, 2.8 h apart. In order to achieve steady-state conditions codeine 60 mg was then taken every 8 h for a further five doses. The plasma concentrations of codeine and morphine after the first, second and seventh doses were analyzed by GC-MS. The maximum plasma concentrations of codeine and morphine were reached about 1 h after administration and this time interval did not change on repeated administration. The peak plasma codeine was higher after the second dose of codeine than after the first and the concentration resembled that at steady-state. For morphine, the plasma concentration did not increase significantly after the second dose. Both after a single dose and during steady-state the plasma concentration of morphine was only 2–3% of that of codeine. It seems unlikely that morphine plays a significant role in the analgesic efficacy of single or repeated doses of codeine.
    Type of Medium: Electronic Resource
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