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Similar Maximum Systemic but not Local Cyclooxygenase-2 Inhibition by 50 mg Lumiracoxib and 90 mg Etoricoxib: A Randomized Controlled Trial in Healthy Subjects

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Abstract

Purpose

Once daily doses of 100–400 mg lumiracoxib have been proposed to inhibit local prostaglandin synthesis longer than systemic prostaglandin synthesis due to local accumulation in inflamed, acidic tissue. Lower, less toxic doses, however, might still achieve the clinical goal and merit further contemplation.

Methods

In a randomized, double-blind, placebo-controlled, three-way cross-over study, 18 healthy men received, with an interval of 24 h, two oral doses of 50 mg lumiracoxib or for comparison, 90 mg etoricoxib, for which local tissue accumulation has not been claimed as therapeutic component. Systemic and local drug concentrations, assessed by means of subcutaneous in-vivo microdialysis, were related to COX-2 inhibiting effects, quantified as inhibition of prostaglandin ex-vivo production in whole blood as well as local tissue prostaglandin (PG) concentrations.

Results

Twenty-four hours after the first dose, only etoricoxib was detectable in plasma and inhibited PGE2 production. In contrast, after the second dose, systemic PGE2 concentrations were significantly reduced by both coxibs, indicating similar maximum systemic effects of the selected doses. The local COX-2 inhibition by etoricoxib was most pronounced for PGD2. To the contrary, no indication was given of local inhibition of PG production by lumiracoxib at the dose tested.

Conclusions

Doses of 50 mg lumiracoxib and 90 mg etoricoxib produced similar maximum inhibition of systemic COX-2 function whereas 50 mg lumiracoxib was ineffective in producing local COX-2 inhibition. At a 50 mg dosage, lumiracoxib does not provide peripheral effects that outlast its systemic actions in therapies of rheumatic diseases such as osteoarthritis.

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Acknowledgments And Disclosures

Lisa Felden and Carmen Walter contributed equally. We thank Prof. Michael Parnham for manuscript language editing. A preliminary report on part of the results has been presented as a conference abstract (Naunyn Schmiedebergs Arch Pharmacol 2011(383), Suppl 1, page 75).

The authors have declared that no competing interests exist. This study was sponsored by the Deutsche Arthrose-Hilfe, Saarlouis, Germany. Additional support was also obtained for the analytical procedures by Deutsche Forschungsgemeinschaft, SFB 1039/Z1 (GG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Author notes

  1. Lisa Felden

    Present address: Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Klinik, Ludwig-Erhard-Straße 100, Wiesbaden, Germany

  2. Nils von Hentig

    Present address: HIVCENTER, Goethe University, Theodor Stern Kai 7, 60590, Frankfurt, Germany

Authors and Affiliations

  1. Institute of Clinical Pharmacology, Goethe University, Theodor Stern Kai 7, 60590, Frankfurt am Main, Germany

    Lisa Felden, Carmen Walter, Carlo Angioni, Yannick Schreiber, Nils von Hentig, Nerea Ferreiros, Gerd Geisslinger & Jörn Lötsch

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  1. Lisa Felden
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Correspondence to Jörn Lötsch.

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Felden, L., Walter, C., Angioni, C. et al. Similar Maximum Systemic but not Local Cyclooxygenase-2 Inhibition by 50 mg Lumiracoxib and 90 mg Etoricoxib: A Randomized Controlled Trial in Healthy Subjects. Pharm Res 31, 1813–1822 (2014). https://doi.org/10.1007/s11095-013-1285-z

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  • DOI: https://doi.org/10.1007/s11095-013-1285-z

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