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Lack of Effect of Omeprazole or of an Aluminium Hydroxide/Magnesium Hydroxide Antacid on the Pharmacokinetics of Lumiracoxib

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Abstract

Objective: To evaluate the effects of multiple doses of omeprazole and of a single dose of an aluminium hydroxide/magnesium hydroxide (Al/Mg) antacid on the single-dose plasma pharmacokinetics of lumiracoxib.

Study Design: Open-label, randomised, three-period, crossover study.

Population Studied: Healthy subjects aged 18–65 years.

Methods: Fourteen subjects who met eligibility criteria were each administered three treatments in random order: (A) lumiracoxib 400mg as a single oral dose; (B) oral omeprazole 20mg once daily for 4 consecutive days, then lumiracoxib 400mg as a single oral dose just prior to oral omeprazole 20mg on day 5; and (C) lumiracoxib 400mg as a single oral dose immediately prior to a 20mL dose of Al/Mg antacid (magnesium hydroxide 800mg and aluminium hydroxide 900mg). The interval between each lumiracoxib dose was 7 days. Analysis of variance was performed to determine whether lumiracoxib alone differed from lumiracoxib plus omeprazole or from lumiracoxib plus Al/Mg antacid for overall exposure (area under the concentration-time curve from zero to infinity [AUC∞]) and peak concentration (Cmax), with treatment sequence, subject, period and treatment as factors. Ratios of geometric means between lumiracoxib plus omeprazole and lumiracoxib plus Al/Mg antacid to lumiracoxib alone (reference) were calculated for AUC∞ and Cmax. If the mean ratios, with 90% CIs, fell within the interval 0.80–1.25, the treatments were considered equivalent.

Results: Arithmetic mean plasma lumiracoxib concentration-time profiles were similar for all treatments, with a rapid rise in concentration after administration, reaching Cmax values (mean ± SD) of 9.24 ± 1.96, 8.81 ± 2.30, and 10.43 ± 3.24 mg/L within 2–3 hours for treatments A, B and C, respectively. AUC∞ was similar for the three treatments (36.75 ± 7.73, 34.88 ± 8.40 and 35.50 ± 5.72 mg • h/L). All ratios of geometric means with 90% CIs fell within the interval used for establishing bioequivalence, except for the Cmax comparison between lumiracoxib plus Al/Mg antacid and lumiracoxib alone, which was 1.11 (0.95, 1.31).

Conclusion: Coadministration of lumiracoxib with omeprazole or with an Al/Mg antacid had no clinically significant effect on lumiracoxib single-dose plasma pharmacokinetics. Lumiracoxib can, therefore, be administered concurrently with either of these agents without need for lumiracoxib dosage alteration.

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  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this study.

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Authors and Affiliations

  1. Department of Exploratory Clinical Development, Novartis Pharmaceuticals, Horsham, UK

    Graham Scott

  2. Departments of Exploratory Clinical Development, Bioanalytics, and Biostatistics, Novartis Pharmaceuticals, East Hanover, New Jersey, USA

    Christine Vinluan Reynolds, Slavica Milosavljev & Wayne Langholff

  3. MDS Pharma Services, Neptune, New Jersey, USA

    Magdy Shenouda

  4. Department of Exploratory Clinical Development, Novartis Pharmaceuticals, Basel, WSJ 210-313, 4002, Switzerland

    Christiane Rordorf

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Scott, G., Reynolds, C.V., Milosavljev, S. et al. Lack of Effect of Omeprazole or of an Aluminium Hydroxide/Magnesium Hydroxide Antacid on the Pharmacokinetics of Lumiracoxib. Clin Pharmacokinet 43, 341–348 (2004). https://doi.org/10.2165/00003088-200443050-00006

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