The effect of quinidine on the analgesic effect of codeine

S. H. Sindrup*, L. Arendt-Nielsen, K. Brøsen, P. Bjerring, H. R. Angelo, B. Eriksen, L. F. Gram

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Clinical Pharmacology
Vol/bind42
Udgave nummer6
Sider (fra-til)587-591
Antal sider5
ISSN0031-6970
DOI
StatusUdgivet - 1. jun. 1992

Fingeraftryk

Quinidine
Placebos
Pain Threshold
Morphine
Cytochrome P-450 CYP2D6
Oxygenases
Cross-Over Studies

Citer dette

Sindrup, S. H. ; Arendt-Nielsen, L. ; Brøsen, K. ; Bjerring, P. ; Angelo, H. R. ; Eriksen, B. ; Gram, L. F. / The effect of quinidine on the analgesic effect of codeine. I: European Journal of Clinical Pharmacology. 1992 ; Bind 42, Nr. 6. s. 587-591.
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Sindrup, SH, Arendt-Nielsen, L, Brøsen, K, Bjerring, P, Angelo, HR, Eriksen, B & Gram, LF 1992, 'The effect of quinidine on the analgesic effect of codeine', European Journal of Clinical Pharmacology, bind 42, nr. 6, s. 587-591. https://doi.org/10.1007/BF00265920

The effect of quinidine on the analgesic effect of codeine. / Sindrup, S. H.; Arendt-Nielsen, L.; Brøsen, K.; Bjerring, P.; Angelo, H. R.; Eriksen, B.; Gram, L. F.

I: European Journal of Clinical Pharmacology, Bind 42, Nr. 6, 01.06.1992, s. 587-591.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - The effect of quinidine on the analgesic effect of codeine

AU - Sindrup, S. H.

AU - Arendt-Nielsen, L.

AU - Brøsen, K.

AU - Bjerring, P.

AU - Angelo, H. R.

AU - Eriksen, B.

AU - Gram, L. F.

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