Diclofenac does not interact with codeine metabolism in vivo: A study in healthy volunteersReportar como inadecuado

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BMC Clinical Pharmacology

, 2:2

First Online: 27 February 2002Received: 05 November 2001Accepted: 27 February 2002


BackgroundPreviously, we have demonstrated a marked inhibition of codeine glucuronidation by diclofenac in human liver tissue homogenate. We therefore aimed to investigate whether diclofenac inhibits glucuronidation of codeine also in vivo in healthy volunteers.

MethodsIn a randomised, placebo-controlled, double-blind, cross-over study, 12 healthy volunteers received a singe of 100 mg codeine phosphate plus 50 mg diclofenac sodium or codeine phosphate plus placebo. Over a 36 hour period serum concentrations of codeine and its metabolites as well as urinary excretion were analysed using LC-mass spectrometry. Side effects were recorded and analgesic efficacy was determined using the cold pressor test 0–6 h.

ResultsA single dose of diclofenac did not alter the formation of codeine-6-glucuronide in healthy volunteers. Metabolic clearance of codeine to morphine was not affected by diclofenac. In terms of side effects, both treatments were well tolerated. Diclofenac did not significantly influence the analgesic effects of codeine in the cold pressor test.

ConclusionsIn contrast to recent in vitro data, a single oral dose of diclofenac did not alter the glucuronidation of codeine in healthy volunteers.

List of abbreviations usedCIconfidence interval

MRmetabolic ratio

NSAIDsnon steroidal anti-inflammatory drugs




Electronic supplementary materialThe online version of this article doi:10.1186-1472-6904-2-2 contains supplementary material, which is available to authorized users.

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Autor: Susanne Ammon - Claudia Marx - Christoph Behrens - Ute Hofmann - Thomas Mürdter - Ernst-Ulrich Griese - Gerd Mikus

Fuente: https://link.springer.com/

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