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Br J Clin Pharmacol. 2014 Jul;78(1):118-28. doi: 10.1111/bcp.12313.

Relationship between inflammation and infliximab pharmacokinetics in rheumatoid arthritis.

Author information

1
Université François Rabelais de Tours, GICC, Tours, France; CNRS, UMR 7293, Tours, France; CHRU de Tours, Tours, France.

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.

KEYWORDS:

inflammation; infliximab; monoclonal antibodies; pharmacokinetics; rheumatoid arthritis

PMID:
24354889
PMCID:
PMC4168386
DOI:
10.1111/bcp.12313
[Indexed for MEDLINE]
Free PMC Article

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