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 400 mg as a single oral dose; (B) oral omeprazole 20 mg once daily for 4 consecutive days, then lumiracoxib 400 mg as a single oral dose just prior to oral omeprazole 20 mg on day 5; and (C) lumiracoxib 400 mg as a single oral dose immediately prior to a 20 mL dose of Al/Mg antacid (magnesium hydroxide 800 mg and aluminium hydroxide 900 mg). 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( infinity )]) 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( infinity ) 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( infinity ) 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.
RCT Entities:
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 400 mg as a single oral dose; (B) oral omeprazole 20 mg once daily for 4 consecutive days, then lumiracoxib 400 mg as a single oral dose just prior to oral omeprazole 20 mg on day 5; and (C) lumiracoxib 400 mg as a single oral dose immediately prior to a 20 mL dose of Al/Mg antacid (magnesium hydroxide 800 mg and aluminium hydroxide 900 mg). 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( infinity )]) 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( infinity ) 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( infinity ) 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.