title: Tocilizumab has no clinically relevant effects on methotrexate pharmacokinetics in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To assess the effects of tocilizumab on methotrexate and 7-hydroxymethotrexate pharmacokinetics in patients with rheumatoid arthritis and to explore the pharmacodynamic effect of tocilizumab on C-reactive protein (CRP), a marker of inflammation.
  
  
  METHODS
  Methotrexate (10 - 25 mg) was administered orally on Days 1, 8, 15, 22, 29, 36, and 43. On Day 8 patients received 10 mg/kg tocilizumab intravenously. Blood samples for pharmacokinetic analyses were collected on Days 1, 15, and 43 and for pharmacodynamics (CRP) throughout the study.
  
  
  RESULTS
  90% CIs for mean effect ratios (Day 15/Day 1 and Day 43/Day 1) of methotrexate and 7-hydroxymethotrexate (AUClast and Cmax) were close to or within the bioequivalence boundaries (80 - 125%). CRP normalized within 1 week after tocilizumab injection and remained within normal limits for 3 weeks.
  
  
  CONCLUSIONS
  Tocilizumab and methotrexate can be administered concurrently without dosage adjustments.
authors.affiliation: F. Hoffmann-La Roche AG, Basel, Switzerland. christophe.schmitt@roche.com
authors.forename: Christophe
authors.initials: C
authors.lastname: Schmitt
authors.forename: Barbara
authors.initials: B
authors.lastname: Kuhn
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Alan
authors.initials: A
authors.lastname: Kivitz
authors.forename: Susan
authors.initials: S
authors.lastname: Grange
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000032:analysis; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000493:pharmacokinetics*; D008875:Middle Aged
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D002097:C-Reactive Protein; C502936:tocilizumab; D008727:Methotrexate