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The effect of quinidine on the analgesic effect of codeine

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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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Authors and Affiliations

  1. Department of Clinical Pharmacology, Odense University, Denmark

    S. H. Sindrup, K. Brøsen & L. F. Gram

  2. Department of Medical Informatics, Aalborg University, Denmark

    L. Arendt-Nielsen

  3. Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark

    P. Bjerring

  4. Department of Clinical Chemistry, Bispebjerg Hospital, Copenhagen, Denmark

    H. R. Angelo

  5. DAK-Laboratoriet a/s, Copenhagen, Denmark

    B. Eriksen

Authors
  1. S. H. Sindrup
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  2. L. Arendt-Nielsen
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  3. K. Brøsen
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  4. P. Bjerring
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  5. H. R. Angelo
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  6. B. Eriksen
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  7. L. F. Gram
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Sindrup, S.H., Arendt-Nielsen, L., Brøsen, K. et al. The effect of quinidine on the analgesic effect of codeine. Eur J Clin Pharmacol 42, 587–591 (1992). https://doi.org/10.1007/BF00265920

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  • DOI: https://doi.org/10.1007/BF00265920

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