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

Authors: Scott G.¹; Christine Vinluan Reynolds²; Milosavljev S.²; Langholff W.²; Shenouda M.³; Rordorf C.⁴

Source: Clinical Pharmacokinetics, Volume 43, Number 5, 2004 , pp. 341-348(8)

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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 (C_max), 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 C_max. 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 C_max 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 C_max comparison between lumiracoxib plus Al/Mg antacid and lumiracoxib alone, which was 1.11 (0.95, 1.31).

Conclusions: 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.

Keywords: Antiulcers, drug interactions; Drug interactions; Omeprazole, drug interactions; Aluminium hydroxide/magnesium hydroxide, drug inte; Cyclo oxygenase inhibitors, drug interactions; Lumiracoxib, drug interactions; Research and development

Document Type: Research article

Affiliations: 1: 1 Department of Exploratory Clinical Development, Novartis Pharmaceuticals, Horsham, UK 2: 2 Departments of Exploratory Clinical Development, Bioanalytics, and Biostatistics, Novartis Pharmaceuticals, East Hanover, New Jersey, USA 3: 3 MDS Pharma Services, Neptune, New Jersey, USA 4: 4 Department of Exploratory Clinical Development, Novartis Pharmaceuticals, Basel, Switzerland

Publication date: 2004-01-01

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

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