Relationship between inflammation and infliximab pharmacokinetics in rheumatoid arthritis

Abstract

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. © 2013 The British Pharmacological Society.