title: Celecoxib, a specific COX-2 inhibitor, has no significant effect on methotrexate pharmacokinetics in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To determine the effects of celecoxib, a specific inhibitor of cyclooxygenase 2 (COX-2) on the renal clearance and plasma pharmacokinetic profile of stable methotrexate (MTX) doses in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Fourteen adult female patients with RA taking a stable weekly dose of MTX (5 to 15 mg/wk) for a minimum of 3 months were randomized to receive concomitantly either celecoxib (200 mg BID) or placebo for a period of 7 days in a single blind, 2 period crossover study of MTX pharmacokinetics and renal clearance.
  
  
  RESULTS
  The plasma pharmacokinetic profile of MTX did not change significantly when celecoxib or a placebo was coadministered. The mean renal clearance of MTX alone, 7.98+/-2.18 l/h, was virtually unchanged by coadministration of celecoxib (7.94+/-1.61 l/h) or placebo (7.97+/-1.19 l/h).
  
  
  CONCLUSIONS
  Celecoxib has no significant effect on the pharmacokinetics or renal clearance of MTX in patients with RA, although these results should be confirmed in prospective studies of elderly and renally impaired patients.
authors.affiliation: Searle Research and Development, Skokie, Illinois 60077, USA. aziz.karim@monsanto.com
authors.forename: A
authors.initials: A
authors.lastname: Karim
authors.forename: D S
authors.initials: DS
authors.lastname: Tolbert
authors.forename: T L
authors.initials: TL
authors.lastname: Hunt
authors.forename: R C
authors.initials: RC
authors.lastname: Hubbard
authors.forename: K M
authors.initials: KM
authors.lastname: Harper
authors.forename: G S
authors.initials: GS
authors.lastname: Geis
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology; D000068579:Celecoxib; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007668:Kidney / Q000502:physiology; D008297:Male; D008565:Membrane Proteins; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology; D011720:Pyrazoles; D016037:Single-Blind Method; D013449:Sulfonamides / Q000008:administration & dosage*; D014556:Urine
chemical_list: D018501:Antirheumatic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D008727:Methotrexate