Lumiracoxib does not affect methotrexate pharmacokinetics in rheumatoid arthritis patients

Ann Pharmacother. 2004 Oct;38(10):1582-7. doi: 10.1345/aph.1E044. Epub 2004 Aug 31.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antirheumatic Agents / blood
  • Antirheumatic Agents / pharmacokinetics*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Cross-Over Studies
  • Cyclooxygenase 2
  • Diclofenac / analogs & derivatives
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Interactions
  • Female
  • Humans
  • Isoenzymes / antagonists & inhibitors*
  • Male
  • Membrane Proteins
  • Methotrexate / analogs & derivatives*
  • Methotrexate / blood
  • Methotrexate / pharmacokinetics*
  • Methotrexate / therapeutic use
  • Middle Aged
  • Organic Chemicals / pharmacology*
  • Organic Chemicals / therapeutic use
  • Prostaglandin-Endoperoxide Synthases


  • Antirheumatic Agents
  • Isoenzymes
  • Membrane Proteins
  • Organic Chemicals
  • Diclofenac
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • lumiracoxib
  • 7-hydroxymethotrexate
  • Methotrexate