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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 less than 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.
S H Sindrup, and
K Brøsen, and
P Bjerring, and
L Arendt-Nielsen, and
U Larsen, and
H R Angelo, and
L F Gram
April 2002,
Journal of clinical psychopharmacology,
S H Sindrup, and
K Brøsen, and
P Bjerring, and
L Arendt-Nielsen, and
U Larsen, and
H R Angelo, and
L F Gram
February 1999,
Pharmacogenetics,
S H Sindrup, and
K Brøsen, and
P Bjerring, and
L Arendt-Nielsen, and
U Larsen, and
H R Angelo, and
L F Gram
February 1991,
Ugeskrift for laeger,
S H Sindrup, and
K Brøsen, and
P Bjerring, and
L Arendt-Nielsen, and
U Larsen, and
H R Angelo, and
L F Gram
February 1994,
The Journal of pharmacology and experimental therapeutics,
S H Sindrup, and
K Brøsen, and
P Bjerring, and
L Arendt-Nielsen, and
U Larsen, and
H R Angelo, and
L F Gram
April 1987,
Pharmacology & toxicology,
S H Sindrup, and
K Brøsen, and
P Bjerring, and
L Arendt-Nielsen, and
U Larsen, and
H R Angelo, and
L F Gram
October 1997,
Pharmacogenetics,
S H Sindrup, and
K Brøsen, and
P Bjerring, and
L Arendt-Nielsen, and
U Larsen, and
H R Angelo, and
L F Gram
January 1990,
Clinical pharmacology and therapeutics,
S H Sindrup, and
K Brøsen, and
P Bjerring, and
L Arendt-Nielsen, and
U Larsen, and
H R Angelo, and
L F Gram
August 1985,
Clinical pharmacology and therapeutics,
S H Sindrup, and
K Brøsen, and
P Bjerring, and
L Arendt-Nielsen, and
U Larsen, and
H R Angelo, and
L F Gram
July 2006,
European journal of clinical pharmacology,
S H Sindrup, and
K Brøsen, and
P Bjerring, and
L Arendt-Nielsen, and
U Larsen, and
H R Angelo, and
L F Gram
January 2017,
European journal of pain (London, England),
