Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine

Søren H. Sindrup*, Kim Brøsen, Peter Bjerring, Lars Arendt-Nielsen, Ulla Larsen, Helle R. Angelo, Lars F. Gram

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    Abstrakt

    The analgesic efficacy and kinetics of a single oral dose of 75 mg codeine was investigated in 12 extensive metabolizers and 12 poor metabolizers of sparteine in a double-blind, placebo-controlled crossover study. The cosegregation of the O-demethylation of codeine to morphine with the sparteine oxidation polymorphism was confirmed. Hence morphine could not be detected in the plasma of any of the poor metabolizers, whereas detectable morphine plasma levels were found in 10 of 12 extensive metabolizers. Pain thresholds to laser stimuli were determined before drug intake and 90, 150, and 210 minutes after drug intake. Codeine significantly increased the pricking pain thresholds in the extensive metabolizers (p < 0.05), whereas there were no significant changes in the poor metabolizers. No change in pain thresholds occurred with placebo in any of the two phenotypes. In the extensive metabolizers there was a significant positive correlation between the increase in pain threshold and plasma concentration of codeine. The study supports the hypothesis that morphine formation is essential for achievement of analgesia during codeine treatment.

    OriginalsprogEngelsk
    TidsskriftClinical Pharmacology and Therapeutics
    Vol/bind48
    Udgave nummer6
    Sider (fra-til)686-693
    Antal sider8
    ISSN0009-9236
    DOI
    StatusUdgivet - dec. 1990

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