The effect of quinidine on the analgesic effect of codeine

Eur J Clin Pharmacol. 1992;42(6):587-91. doi: 10.1007/BF00265920.


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 pinprick 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 (less than 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Codeine / blood
  • Codeine / pharmacology*
  • Double-Blind Method
  • Drug Interactions
  • Female
  • Humans
  • Male
  • Morphine / blood
  • Pain Measurement / drug effects*
  • Pain Measurement / methods
  • Quinidine / blood
  • Quinidine / pharmacology*


  • Morphine
  • Quinidine
  • Codeine