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Diclofenac does not interact with codeine metabolism in vivo: a study in healthy volunteers.

Ammon S, Marx C, Behrens C, Hofmann U, Mürdter T, Griese EU, Mikus G - BMC Clin Pharmacol (2002)

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

View Article: PubMed Central - HTML - PubMed

Affiliation: Internal Medicine VI - Clinical Pharmacology and Pharmacoepidemiology, University Hospital, Heidelberg, Germany. susanne.ammon@medizin.uni-magdeburg.de

ABSTRACT

Background: Previously, 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.

Methods: In 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).

Results: A 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.

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

Show MeSH
Serum concentration time profile of codeine and codeine-6-glucuronide after administration of codeine + placebo vs. codeine + diclofenac (Mean, SD, n= 12) □ codeine + placebo ♦ codeine + diclofenac
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Figure 2: Serum concentration time profile of codeine and codeine-6-glucuronide after administration of codeine + placebo vs. codeine + diclofenac (Mean, SD, n= 12) □ codeine + placebo ♦ codeine + diclofenac

Mentions: Similar serum concentrations of codeine and its metabolite C-6-G were observed after treatment with codeine + placebo vs. codeine + diclofenac (Figure 2). Peak serum concentrations (Cmax) of codeine (764; 602–924 pmol ml-1 vs. 821; 663–980 pmol ml-1) and C-6-G (5263; 4738–5788 pmol ml-1 vs. 5621; 5167–6074 pmol ml-1), did not differ significantly between the two different treatments, nor did the time to attain peak serum concentrations (tmax) and the terminal half-life t1/2 (Table 1). The concentrations of codeine and its metabolites in the one intermediate metaboliser (MR = 2.8) were within the range of the concentrations of the other volunteers with MR<1, however as expected the metabolites formed via O-demethylation (morphine, morphine glucuronides and normorphine) were the lowest or second lowest observed.


Diclofenac does not interact with codeine metabolism in vivo: a study in healthy volunteers.

Ammon S, Marx C, Behrens C, Hofmann U, Mürdter T, Griese EU, Mikus G - BMC Clin Pharmacol (2002)

Serum concentration time profile of codeine and codeine-6-glucuronide after administration of codeine + placebo vs. codeine + diclofenac (Mean, SD, n= 12) □ codeine + placebo ♦ codeine + diclofenac
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC101395&req=5

Figure 2: Serum concentration time profile of codeine and codeine-6-glucuronide after administration of codeine + placebo vs. codeine + diclofenac (Mean, SD, n= 12) □ codeine + placebo ♦ codeine + diclofenac
Mentions: Similar serum concentrations of codeine and its metabolite C-6-G were observed after treatment with codeine + placebo vs. codeine + diclofenac (Figure 2). Peak serum concentrations (Cmax) of codeine (764; 602–924 pmol ml-1 vs. 821; 663–980 pmol ml-1) and C-6-G (5263; 4738–5788 pmol ml-1 vs. 5621; 5167–6074 pmol ml-1), did not differ significantly between the two different treatments, nor did the time to attain peak serum concentrations (tmax) and the terminal half-life t1/2 (Table 1). The concentrations of codeine and its metabolites in the one intermediate metaboliser (MR = 2.8) were within the range of the concentrations of the other volunteers with MR<1, however as expected the metabolites formed via O-demethylation (morphine, morphine glucuronides and normorphine) were the lowest or second lowest observed.

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

View Article: PubMed Central - HTML - PubMed

Affiliation: Internal Medicine VI - Clinical Pharmacology and Pharmacoepidemiology, University Hospital, Heidelberg, Germany. susanne.ammon@medizin.uni-magdeburg.de

ABSTRACT

Background: Previously, 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.

Methods: In 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).

Results: A 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.

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

Show MeSH