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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 morphine, morphine-3- and morphine-6-glucuronide after administration of codeine + placebo vs. codeine + diclofenac (Mean, SD, n= 12) □ codeine + placebo ♦ codeine + diclofenac
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Figure 3: Serum concentration time profile of morphine, morphine-3- and morphine-6-glucuronide after administration of codeine + placebo vs. codeine + diclofenac (Mean, SD, n= 12) □ codeine + placebo ♦ codeine + diclofenac

Mentions: Peak serum concentrations (Cmax) of morphine (22.4 pmol ml-1; 12.3–32.5 95% CI vs. 24.3 pmol ml-1; 13.7–35.0 95% CI) and M-6-G (63.4 pmol ml-1; 38.7–88.1 95% CI vs. 68.8 pmol ml-1; 41.2–96.5 95% CI) did not differ significantly between the two different treatments, as well as the time to attain peak serum concentrations (tmax) and the terminal half-life t1/2 (Table 1). AUC of morphine did not differ between the two treatments (Table 2). A small but significant increase of the AUC of M-6-G (+10.8%) was observed after codeine + diclofenac (Table 2). Serum concentration-time curves of morphine, M-3-G and M-6-G are displayed in Figure 3.


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 morphine, morphine-3- and morphine-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 3: Serum concentration time profile of morphine, morphine-3- and morphine-6-glucuronide after administration of codeine + placebo vs. codeine + diclofenac (Mean, SD, n= 12) □ codeine + placebo ♦ codeine + diclofenac
Mentions: Peak serum concentrations (Cmax) of morphine (22.4 pmol ml-1; 12.3–32.5 95% CI vs. 24.3 pmol ml-1; 13.7–35.0 95% CI) and M-6-G (63.4 pmol ml-1; 38.7–88.1 95% CI vs. 68.8 pmol ml-1; 41.2–96.5 95% CI) did not differ significantly between the two different treatments, as well as the time to attain peak serum concentrations (tmax) and the terminal half-life t1/2 (Table 1). AUC of morphine did not differ between the two treatments (Table 2). A small but significant increase of the AUC of M-6-G (+10.8%) was observed after codeine + diclofenac (Table 2). Serum concentration-time curves of morphine, M-3-G and M-6-G are displayed in Figure 3.

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