title: Relationship between inflammation and infliximab pharmacokinetics in rheumatoid arthritis.
abstract: OBJECTIVE
  Infliximab, an anti-tumour necrosis factor-α monoclonal antibody, is indicated in rheumatoid arthritis (RA). Our objective was to evaluate the influence of the sources of infliximab pharmacokinetic variability in RA.
  
  
  METHODS
  Eighty-four patients treated with infliximab for RA were included in a prospective noncomparative study. They were analysed between two consecutive infliximab infusions. Infliximab concentrations were measured before the infusion, 2 h, 1 and 4 weeks after the infusion and immediately before the next infusion. Infliximab concentrations were described using a two-compartment population pharmacokinetic model.
  
  
  RESULTS
  The mean (interindividual standard deviation) estimated central volume of distribution was 2.3 l (36%) and systemic clearance was 0.019 l h(-1) (37%). The central volume of distribution increased with bodyweight; it was doubled between 50 and 90 kg. Systemic clearance increased with pre-infusion C-reactive protein concentration by 20%, varying from 3 to 14 mg l(-) 1, and was decreased by 30% when methotrexate was coadministered.
  
  
  CONCLUSIONS
  The influence of methotrexate and inflammation on infliximab clearance suggests that individual adjustment of infliximab doses according to disease activity may be useful in RA.
authors.affiliation: Université François Rabelais de Tours, GICC, Tours, France; CNRS, UMR 7293, Tours, France; CHRU de Tours, Tours, France.
authors.forename: David
authors.initials: D
authors.lastname: Ternant
authors.forename: Emilie
authors.initials: E
authors.lastname: Ducourau
authors.forename: Aleth
authors.initials: A
authors.lastname: Perdriger
authors.forename: Anca
authors.initials: A
authors.lastname: Corondan
authors.forename: Benoît
authors.initials: B
authors.lastname: Le Goff
authors.forename: Valérie
authors.initials: V
authors.lastname: Devauchelle-Pensec
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Solau-Gervais
authors.forename: Hervé
authors.initials: H
authors.lastname: Watier
authors.forename: Philippe
authors.initials: P
authors.lastname: Goupille
authors.forename: Gilles
authors.initials: G
authors.lastname: Paintaud
authors.forename: Denis
authors.initials: D
authors.lastname: Mulleman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology; D008875:Middle Aged; D008954:Models, Biological; D011241:Prednisone / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D002097:C-Reactive Protein; D000069285:Infliximab; D011241:Prednisone; D008727:Methotrexate
keywords: inflammation; infliximab; monoclonal antibodies; pharmacokinetics; rheumatoid arthritis