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Ann Pharmacother. 2004 Oct;38(10):1582-7. Epub 2004 Aug 31.

Lumiracoxib does not affect methotrexate pharmacokinetics in rheumatoid arthritis patients.

Author information

1
Exploratory Clinical Development, Novartis Pharma AG, Basel, Switzerland. stefan.hartmann@pharma.novartis.com

Abstract

BACKGROUND:

Methotrexate and nonsteroidal antiinflammatory drugs are frequently coadministered in the treatment of rheumatoid arthritis (RA).

OBJECTIVE:

To evaluate the effect of lumiracoxib, a novel cyclooxygenase-2 selective inhibitor, on methotrexate pharmacokinetics and short-term safety in patients with RA.

METHODS:

This multicenter, randomized, double-blind, placebo-controlled crossover study enrolled 18 patients (mean age 49.1 y) with stable RA. Patients were randomized to receive methotrexate 7.5-15 mg orally once weekly plus either lumiracoxib 400 mg/day or placebo for 7 days. Patients then received the other treatment combination for an additional 7 days. Serial blood and urine were collected for 24 hours after the methotrexate dose on day 1 (methotrexate alone) and days 8 and 15 (combination treatment).

RESULTS:

Plasma methotrexate pharmacokinetics (AUC(0-t), maximum concentration [C(max)], time to C(max)) and methotrexate protein binding were similar for methotrexate alone (108.0 ng.h/mL, 26.7 ng/mL, 1.5 h, and 57.1%, respectively), methotrexate/lumiracoxib (110.2 ng.h/mL, 27.5 ng/mL, 1.0 h, and 53.7%, respectively), and methotrexate/placebo (101.8 ng.h/mL, 22.6 ng/mL, 1.0 h, and 57.0%, respectively). Similarly, no clinically significant difference was found in the urinary excretion of methotrexate. Mean exposure to the 7-OH metabolite was lower when methotrexate was given with lumiracoxib compared with placebo, shown by a reduction in AUC and C(max), although similar amounts of the metabolite were recovered in urine following both lumiracoxib and placebo. Coadministration of methotrexate and lumiracoxib was well tolerated.

CONCLUSIONS:

Lumiracoxib had no significant effect on the pharmacokinetics, protein binding, or urinary excretion of coadministered methotrexate in patients with RA.

PMID:
15340127
DOI:
10.1345/aph.1E044
[Indexed for MEDLINE]

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