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Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine
Author(s) -
Sindrup Søren H,
Brøsen Kim,
Bjerring Peter,
ArendtNielsen Lars,
Larsen Ulla,
Angelo Helle R,
Gram Lars F
Publication year - 1990
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1990.212
Subject(s) - codeine , morphine , analgesic , placebo , anesthesia , pharmacology , medicine , crossover study , debrisoquine , cyp2d6 , metabolism , cytochrome p450 , pathology , alternative medicine
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. Clinical Pharmacology and Therapeutics (1990) 48 , 686–693; doi: 10.1038/clpt.1990.212