The effect of quinidine on the analgesic effect of codeine |
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Authors: | S. H. Sindrup L. Arendt-Nielsen K. Brøsen P. Bjerring H. R. Angelo B. Eriksen L. F. Gram |
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Affiliation: | (1) Department of Clinical Pharmacology, Odense University, Denmark;(2) Department of Medical Informatics, Aalborg University, Denmark;(3) Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark;(4) Department of Clinical Chemistry, Bispebjerg Hospital, Copenhagen, Denmark;(5) DAK-Laboratoriet a/s, Copenhagen, Denmark |
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Abstract: | Summary We have studied the hypoalgesic effect of codeine (100 mg) after blocking the hepatic O-demethylation of codeine to morphine via the sparteine oxygenase (CYP2D6) by quinidine (200 mg). The study was performed in 16 extensive metabolizers of sparteine, using a double-blind, randomized, four-way, cross-over design. The treatments given at 3 h intervals during the four sessions were placebo/placebo, quinidine/placebo, placebo/codeine, and quinidine/codeine. We measured pin-prick pain and pain tolerance thresholds to high energy argon laser stimuli before and 1, 2, and 3 h after codeine or placebo.After codeine and placebo, the peak plasma concentration of morphine was 6–62 (median 18) nmol·.l–1. When quinidine pre-treatment was given, no morphine could be detected (<4 nmol·l–1) after codeine. The pin-prick pain thresholds were significantly increased after placebo/codeine, but not after quinidine/codeine compared with placebo/placebo. Both placebo/codeine and quinidine/codeine increased pain tolerance thresholds significantly. Quinidine/codeine and quinidine/placebo did not differ significantly for either pin-prick or tolerance pain thresholds.These results are compatible with local CYP2D6 mediated formation of morphine in the brain, not being blocked by quinidine. Alternatively, a hypoalgesic effect of quinidine might have confounded the results. |
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Keywords: | Codeine Quinidine CYP2D6 hypolagesia drug interaction |
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