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Relationship between inflammation and infliximab pharmacokinetics in rheumatoid arthritis
Author(s) -
Ternant David,
Ducourau Emilie,
Perdriger Aleth,
Corondan Anca,
Le Goff Benoît,
DevauchellePensec Valérie,
SolauGervais Elisabeth,
Watier Hervé,
Goupille Philippe,
Paintaud Gilles,
Mulleman Denis
Publication year - 2014
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12313
Subject(s) - infliximab , rheumatoid arthritis , medicine , methotrexate , pharmacokinetics , volume of distribution , arthritis , nonmem , pharmacology , gastroenterology , population , tumor necrosis factor alpha , environmental health
Aims 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 .