title: The effect of quinidine on the analgesic effect of codeine.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, Odense University, Aalborg University.
authors.forename: S H
authors.initials: SH
authors.lastname: Sindrup
authors.forename: L
authors.initials: L
authors.lastname: Arendt-Nielsen
authors.forename: K
authors.initials: K
authors.lastname: Brøsen
authors.forename: P
authors.initials: P
authors.lastname: Bjerring
authors.forename: H R
authors.initials: HR
authors.lastname: Angelo
authors.forename: B
authors.initials: B
authors.lastname: Eriksen
authors.forename: L F
authors.initials: LF
authors.lastname: Gram
mesh_terms: D000328:Adult; D003061:Codeine / Q000097:blood / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D009020:Morphine / Q000097:blood; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D011802:Quinidine / Q000097:blood / Q000494:pharmacology*
chemical_list: D009020:Morphine; D011802:Quinidine; D003061:Codeine