Lack of effect of omeprazole or of an aluminium hydroxide/magnesium hydroxide antacid on the pharmacokinetics of lumiracoxib.
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.


METHODS
Open-label, randomised, three-period, crossover study.


METHODS
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.
Scott
Graham
G
Department of Exploratory Clinical Development, Novartis Pharmaceuticals, Horsham, UK. christiane.rordorf@pharma.novartis.com
Vinluan Reynolds
Christine
C
Milosavljev
Slavica
S
Langholff
Wayne
W
Shenouda
Magdy
M
Rordorf
Christiane
C
D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000494:pharmacology*; D000863:Antacids / Q000494:pharmacology*; D019540:Area Under Curve; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2; D004008:Diclofenac / Q000031:analogs & derivatives; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008276:Magnesium Hydroxide / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009853:Omeprazole / Q000494:pharmacology*; D009930:Organic Chemicals / Q000097:blood / Q000493:pharmacokinetics*; D011451:Prostaglandin-Endoperoxide Synthases; D054328:Proton Pump Inhibitors
D000863:Antacids; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009930:Organic Chemicals; D054328:Proton Pump Inhibitors; D004008:Diclofenac; C013591:aluminum hydroxide, magnesium hydroxide, drug combination; D000536:Aluminum Hydroxide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D009853:Omeprazole; D008276:Magnesium Hydroxide; C473384:lumiracoxib